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Cited by 755Oral microbiology and periodontitis researchGut microbiota and healthBacterial biofilms and quorum sensing

The oral microbiome: Role of key organisms and complex networks in oral health and disease

Open access
Sedghi, Lea, DiMassa, Vincent, Harrington, Anthony, Lynch, Susan V., Kapila, Yvonne L.·2021·Periodontology 2000
DOI 10.1111/prd.12393PMC PMC8457218
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Abstract

States of oral health and disease reflect the compositional and functional capacities of, as well as the interspecies interactions within, the oral microbiota. The oral cavity exists as a highly dynamic microbial environment that harbors many distinct substrata and microenvironments that house diverse microbial communities. Specific to the oral cavity, the nonshedding dental surfaces facilitate the development of highly complex polymicrobial biofilm communities, characterized not only by the distinct microbes comprising them, but cumulatively by their activities. Adding to this complexity, the oral cavity faces near‐constant environmental challenges, including those from host diet, salivary flow, masticatory forces, and introduction of exogenous microbes. The composition of the oral microbiome is shaped throughout life by factors including host genetics, maternal transmission, as well as environmental factors, such as dietary habits, oral hygiene practice, medications, and systemic factors. This dynamic ecosystem presents opportunities for oral microbial dysbiosis and the development of dental and periodontal diseases. The application of both in vitro and culture‐independent approaches has broadened the mechanistic understandings of complex polymicrobial communities within the oral cavity, as well as the environmental, local, and systemic underpinnings that influence the dynamics of the oral microbiome. Here, we review the present knowledge and current understanding of microbial communities within the oral cavity and the influences and challenges upon this system that encourage homeostasis or provoke microbiome perturbation, and thus contribute to states of oral health or disease.

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TL;DR

This narrative review summarizes how the oral microbiome’s composition, interspecies networks, and functional activities shape oral health and disease, including caries, periodontal disease, and systemic conditions. It also reviews culture-independent and omics methods, dietary influences, and oral hygiene or probiotic strategies for modulating the oral microbiota.

Key findings

  • The oral microbiome is the second most diverse human microbiota after the colon, with over 700 bacterial species identified; the NIH Human Microbiome Project found the oral microbiome has the largest core set of microbes shared among unrelated individuals across 9 intraoral sites from 200 participants.
  • In the Human Microbiome Project, the main genus at >10% abundance and present in >75% of samples was *Streptococcus*, specifically *S oralis*, *S mitis*, and *S peroris*; other core members at >1% abundance across at least 80% of samples from one or more sites included *Gemella*, *Veillonella*, *Prevotella*, *Fusobacterium*, *Porphyromonas*, *Neisseria*, *Capnocytophaga*, *Corynebacterium*, and *Actinomyces*.
  • Oral disease reflects dysbiosis: caries is linked to high carbohydrate intake, acid production, and aciduric/acidogenic species such as *S mutans* and *Lactobacillus*; periodontal disease involves subgingival dysbiosis and red complex bacteria *T forsythia*, *T denticola*, and *P gingivalis*, with inflammatory tissue destruction.
  • The review links oral microbes to systemic disease, including cardiovascular disease, rheumatoid arthritis, Alzheimer’s disease, adverse pregnancy outcomes, and cancers; it also describes dietary shifts at the Neolithic and Industrial Revolutions as associated with oral microbial changes and increased dental/periodontal disease.

Methods

  • Design: narrative review of current knowledge on oral microbial communities, health/disease states, and modulation strategies.
  • Data/sample: no primary sample; the paper synthesizes findings from in vitro biofilm models, germ-free mouse studies, culture-independent sequencing, metagenomics, metatranscriptomics, metabolomics, proteomics, clinical microbiome studies, and dietary/epidemiologic studies.
  • Main analysis: thematic synthesis of microbial composition, community assembly, biogeography, host–microbe interactions, diet, oral hygiene, and therapeutic approaches.

Limitations

  • Stated in the paper: 16S rRNA biomarker approaches can be limited in resolving phylogenetically related species or strains and do not provide functional gene content; in vitro biofilm models have difficulty recapitulating the complexity of the oral cavity; metabolomics has drawbacks; and mechanistic understanding of diet/fiber effects on the oral microbiome and of microbiota influences on taste remains limited.
  • Evident from the text: as a narrative review, it does not report a systematic search strategy, inclusion/exclusion criteria, or formal risk-of-bias assessment for the cited literature.

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Integrity signals

Registry

Crossref · 10.1111/prd.12393

Cites

315 of 315 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

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  • Interpretationnone given

    States of oral health and disease reflect the compositional and functional capacities of, as well as the interspecies interactions within, the oral microbiota.

    “States of oral health and disease reflect the compositional and functional capacities of, as well as the interspecies interactions within, the oral microbiota.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Toothbrushes themselves can serve as reservoirs for pathogenic bacteria that can then inoculate the oral cavity.

    “Toothbrushes themselves, however, can also serve as reservoirs for pathogenic bacteria that can then inoculate the oral cavity, bringing into view the importance of properly sanitizing and storing personal dental hygiene equipment.28, 33”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Frazelle MR, Munro CL. Toothbrush contamination: a review of the literature. Nurs Res Pract. 2012; 2012: 1‐ 6. PMC3270454 22315679 source

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    • cites [33] Shang Q, Gao Y, Qin T, Wang S, Shi Y, Chen T. Interaction of oral and toothbrush microbiota affects oral cavity health. Front Cell Infect Microbiol. 2020; 10: 17. 32117797 PMC7011102 source

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  • Premisecitation

    Many associations between oral microbes, specifically those implicated in periodontal disease, and other common chronic conditions, such as cardiovascular disease and high blood pressure, have been established.

    “Many associations between oral microbes, specifically those implicated in periodontal disease, and other common chronic conditions, such as cardiovascular disease and high blood pressure, have been established.40”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Olsen I. From the Acta Prize Lecture 2014: The Periodontal‐Systemic Connection Seen from a Microbiological Standpoint: Summary of the Acta Odontologica Scandinavia Price Lecture 2014 Presented at the Meeting of the IADR/Pan European Region in Dubrovnik. September 10–13. 2014. Acta Odontol Scand. 2015; 73(8): 563‐ 568. 25891035 source

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  • Premisecitation

    Recent data indicate that the oral microbiome influences the dietary preferences of its host.

    “While diet influences the oral microbiome,22, 24, 26 recent data indicate that the oral microbiome influences the dietary preferences of its host.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [22] Moye ZD, Zeng L, Burne RA. Fueling the caries process: carbohydrate metabolism and gene regulation by Streptococcus mutans. J Oral Microbiol. 2014; 6(1): 24878. PMC4157138 25317251 source

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    • cites [24] Adler CJ, Dobney K, Weyrich LS, et al. Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the neolithic and industrial revolutions. Nat Genet. 2013; 45(4): 450‐ 455. 10.1038/ng.2536 23416520 PMC3996550 source

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    • cites [26] Woelber JP, Tennert C. Chapter 13: diet and periodontal diseases. Impact Nutr. Diet Oral Health 2020; 28: 125‐ 133. 10.1159/000455380 31940617 source

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  • Interpretationreasoning

    The oral microbiome may serve as a reservoir for pathobionts that can either contribute to or exacerbate disease at remote body niches or organ systems.

    “These data suggest that the oral microbiome may serve as a reservoir for pathobionts that can either contribute to or exacerbate disease at remote body niches or organ systems.”
    Quote in the paperSubstantial claim
  • May combine two claims. 117
  • Classified as probably not a substantial claim. 34

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    Premisecitation

    Pioneer microbial colonizers of the oral cavity, such as Streptococcus mitis, Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus salivarius, can bind selectively to tongue and cheek cells before the teeth emerge and can outcompete other microbial species.

    “Pioneer microbial colonizers of the oral cavity, such as Streptococcus mitis, Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus salivarius, display core characteristics that make them well suited to this specific niche as they are able to bind selectively to tongue and cheek cells before the teeth emerge and can outcompete other microbial species.17, 19”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] Baker JL, Edlund A. Exploiting the oral microbiome to prevent tooth decay: has evolution already provided the best tools? Front Microbiol. 2019; 9: 3323. 30687294 PMC6338091 source

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    • cites [19] Long SS, Swenson R. Determinants of the developing oral flora in normal newborns. Appl Environ Microbiol. 1976; 32(4): 494‐ 497. 791120 PMC170295 source

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    Premisecitation

    Certain bacteria, such as some Clostridia and Prevotella species, have been associated with taste thresholds, such as sweet, sour, salty, and bitter, plausibly representing a mechanism by which the oral microbiota influences dietary preferences.

    “Certain bacteria, such as some Clostridia and Prevotella species, have been associated with taste thresholds, such as sweet, sour, salty, and bitter, plausibly representing a mechanism by which the oral microbiota influences dietary preferences to sustain its membership and persistence in the oral cavity.27, 28”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Cattaneo C, Gargari G, Koirala R, et al. New insights into the relationship between taste perception and oral microbiota composition. Sci Rep. 2019; 9(1): 1‐ 8. 30837660 PMC6401163 source

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    • cites [28] Frazelle MR, Munro CL. Toothbrush contamination: a review of the literature. Nurs Res Pract. 2012; 2012: 1‐ 6. PMC3270454 22315679 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Emerging teeth acquire a protective glycoprotein coat, which initiates successional microbial colonization resulting in the development of complex polymicrobial biofilm communities, namely dental plaque.

    “Emerging teeth acquire a protective glycoprotein coat, which sets in motion successional microbial colonization, resulting in the development of complex polymicrobial biofilm communities, namely dental plaque.20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Rosan B, Lamont RJ. Dental plaque formation. Microbes Infect. 2000; 2(13): 1599‐ 1607. 11113379 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Germ-free mice allow experimentation in mammals with either no pre-existing microbiome or a highly defined microbial background.

    “A major advancement in this domain has been the development of germ‐free mice—animals bred, fed, and raised under sterile conditions—which offer a useful tool for studying the microbiome.46 First conceptualized by Louis Pasteur in 1885 but with uses only fully appreciated in recent decades, this approach allows experimentation in mammals with either no pre‐existing microbiome or a highly defined”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Kennedy EA, King KY, Baldridge MT. Mouse microbiota models: comparing germ‐free mice and antibiotics treatment as tools for modifying gut bacteria. Front Physiol. 2018; 9: 1534. 30429801 PMC6220354 source

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    Premisecitation

    Early research demonstrates that oral cavity-associated microbes can influence immune responses and disease pathogenesis outside the oral cavity, and that their ability to colonize ectopic sites depends on the current state of health of that site.

    “Data on the mechanistic connections involved in the development of disease at sites distant from the oral cavity remain sparse, but early research demonstrates that oral cavity‐associated microbes can influence immune responses and disease pathogenesis outside the oral cavity, and that their ability to colonize ectopic sites depends on the current state of health of that site.39, 41”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Atarashi K, Suda W, Luo C, et al. Ectopic colonization of oral bacteria in the intestine drives Th1 cell induction and inflammation. Science. 2017; 358(6361): 359‐ 365. 29051379 PMC5682622 source

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    • cites [41] d’Ettorre G, Oliva A, DeAngelis M, Vullo VRE. Ectopic colonization of oral bacteria in the intestine drives Th1 cell induction and. Inflammation. Science. 2019; 358: 359‐ 365. PMC5682622 29051379

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    Premisecitation

    Studies using germ-free mice have demonstrated the role of diabetes in disrupting the equilibrium of the oral microbiota and confirmed the role of the oral microbiota in periodontal disease pathogenesis.

    “Studies using germ‐free mice have also been employed in the context of the oral microbiome, demonstrating the role of diabetes in disrupting the equilibrium of the oral microbiota50 and confirming the role of the oral microbiota in periodontal disease pathogenesis.51, 52”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [50] Xiao E, Mattos M, Vieira GHA, et al. Diabetes enhances IL‐17 expression and alters the oral microbiome to increase its pathogenicity. Cell Host Microbe. 2017; 22(1): 120‐ 128.e4. 10.1016/j.chom.2017.06.014 28704648 PMC5701758 source

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    • cites [51] Hajishengallis G, Liang S, Payne MA, et al. Low‐abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011; 10(5): 497‐ 506. 22036469 PMC3221781 source

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    • cites [52] Dutzan N, Kajikawa T, Abusleme L, et al. A dysbiotic microbiome triggers T H 17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018; 10(463): eaat0797. 10.1126/scitranslmed.aat0797 30333238 PMC6330016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Over 250 species from the oral cavity have been isolated in culture and characterized, including key pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans, involved in the etiology of dental caries and periodontal disease.

    “Over 250 species from the oral cavity have been isolated in culture and characterized, including several key pathogens, such as Streptococcus mutans, Porphyromonas gingivalis, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans, involved in the etiology of dental caries and periodontal disease.7, 8, 9”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7] Holt SC, Ebersole JL Porphyromonas Gingivalis, Treponema Denticola, and Tannerella Forsythia: The “red complex”, a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000. 2005; 38: 72‐ 122. 10.1111/j.1600-0757.2005.00113.x 15853938 source

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    • cites [8] Takahashi N. Oral Microbiome metabolism: from “who are they?” To “what are they doing?”. J Dent Res 2015; 94(12): 1628‐ 1637. 10.1177/0022034515606045 26377570 source

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    • cites [9] Wade WG. The oral microbiome in health and disease. Pharmacol Res. 2013; 69(1): 137‐ 143. 10.1016/j.phrs.2012.11.006 23201354 source

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    Premisecitation

    Toothbrushing and flossing can be powerful means to disrupt plaque, the microbial inhabitants of which can cause tooth demineralization and gingival inflammation long-term.

    “Toothbrushing and flossing can be powerful means to disrupt plaque, the microbial inhabitants of which can cause tooth demineralization and gingival inflammation long‐term.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Terezhalmy GT, Bsoul SA, Bartizek RD, Biesbrock AR. Plaque removal efficacy of a prototype manual toothbrush versus an ADA reference manual toothbrush with and without dental floss. J Contemp Dent Pr. 2005; 6(3): 1‐ 13. 16127467 source

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  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The dynamic oral ecosystem presents opportunities for oral microbial dysbiosis and the development of dental and periodontal diseases.

    “This dynamic ecosystem presents opportunities for oral microbial dysbiosis and the development of dental and periodontal diseases.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Diet provides nutritional resources for the oral microbiota and serves as a selective pressure by enriching for organisms best adapted to utilize specific host-derived dietary resources.

    “Diet provides nutritional resources for the oral microbiota and also serves as a selective pressure by enriching for organisms best adapted to utilize specific host‐derived dietary resources.22”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Moye ZD, Zeng L, Burne RA. Fueling the caries process: carbohydrate metabolism and gene regulation by Streptococcus mutans. J Oral Microbiol. 2014; 6(1): 24878. PMC4157138 25317251 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dental plaque matrices create unique microenvironments that harbor acidic and anaerobic microenvironments, and thus select for organisms distinct from those growing directly on the tooth surface.

    “These complex dental plaque matrices create unique microenvironments that harbor acidic and anaerobic microenvironments, and thus select for organisms distinct from those growing directly on the tooth surface.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Kriebel K, Hieke C, Müller‐Hilke B, Nakata M, Kreikemeyer B. Oral biofilms from symbiotic to pathogenic interactions and associated disease‐connection of periodontitis and rheumatic arthritis by peptidylarginine deiminase. Front Microbiol. 2018; 9: 53. 29441048 PMC5797574 source

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    Premisecitation

    Biofilms, with anaerobic centers and aerobic peripheries, exhibit gradients of oxygenation.

    “Biofilms, with anaerobic centers and aerobic peripheries, exhibit gradients of oxygenation.60, 61”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [60] Marsh PD, Bradshaw DJ. Physiological approaches to the control of oral biofilms. Adv Dent Res. 1997; 11(1): 176‐ 185. 9524454 source

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    • cites [61] Mark Welch JL, Rossetti BJ, Rieken CW, Dewhirst FE, Borisy GG. Biogeography of a human oral microbiome at the micron scale. Proc Natl Acad Sci USA. 2016; 113(6): E791‐ E800. 10.1073/pnas.1522149113 26811460 PMC4760785 source

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  • Classified as probably not a substantial claim.

    Premisenone given

    The nonshedding dental surfaces facilitate the development of highly complex polymicrobial biofilm communities, characterized by distinct microbes and their cumulative activities.

    “Specific to the oral cavity, the nonshedding dental surfaces facilitate the development of highly complex polymicrobial biofilm communities, characterized not only by the distinct microbes comprising them, but cumulatively by their activities.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Such hypervariable genes or regions permit identification of microbial community members but can be limited in their capacity to resolve phylogenetically related species or strains and do not provide information on functional gene content.

    “Such hypervariable genes or regions permit identification of microbial community members but can be limited in their capacity to resolve phylogenetically related species or strains and do not provide information on functional gene content of the microbial members present.72”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [72] Poretsky R, Rodriguez‐R LM, Luo C, Tsementzi D, Konstantinidis KT. Strengths and limitations of 16S RRNA gene amplicon sequencing in revealing temporal microbial community dynamics. PLoS One. 2014; 9(4): e93827. 10.1371/journal.pone.0093827 24714158 PMC3979728 source

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    Premisecitation

    Proteomic applications have been applied to understand changes in the proteome that diverge states of periodontal health from disease and to further characterize various periodontal disease states, including gingivitis, mild, moderate, chronic, and aggressive periodontitis.

    “Proteomic applications have been applied to understand changes in the proteome that diverge states of periodontal health from disease and to further characterize various periodontal disease states, including gingivitis, mild, moderate, chronic, and aggressive periodontitis.70, 101, 102, 103, 104”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [70] Silva‐Boghossian CM, Colombo APV, Tanaka M, Rayo C, Xiao Y, Siqueira WL. Quantitative proteomic analysis of gingival crevicular fluid in different periodontal conditions. PLoS One. 2013; 8(10): e75898. 10.1371/journal.pone.0075898 24098404 PMC3787961 source

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    • cites [101] Belstrøm D, Jersie‐Christensen RR, Lyon D, et al. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls. PeerJ. 2016; 4: e2433. 10.7717/peerj.2433 27672500 PMC5028799 source

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    • cites [102] Bostanci N, Belibasakis GN. Gingival crevicular fluid and its immune mediators in the proteomic era. Periodontol 2000. 2018; 76(1): 68‐ 84. 10.1111/prd.12154 29193353 source

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    • cites [103] Rylev M, Abduljabar AB, Reinholdt J, et al. Proteomic and immunoproteomic analysis of aggregatibacter actinomycetemcomitans JP2 clone strain HK1651. J. Proteomics. 2011; 74(12): 2972‐ 2985. 10.1016/j.jprot.2011.07.022 21867783 source

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    • cites [104] Trindade F, Amado F, Oliveira‐Silva RP, et al. Toward the definition of a peptidome signature and protease profile in chronic periodontitis. PROTEOMICS – Clin Appl. 2015; 9(9–10): 917‐ 927. 10.1002/prca.201400191 25669956 source

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    Sequence-based approaches to assess microbial composition include biomarker approaches that focus on a single kingdom-specific ubiquitous microbial gene or region that exhibits sequence hypervariability, such as the 16S ribosomal RNA gene in bacteria or the interspacer region in fungi.

    “Sequence‐based approaches to assess microbial composition include biomarker approaches that focus on a single kingdom‐specific ubiquitous microbial gene or region that exhibits sequence hypervariability (eg, the 16S ribosomal RNA gene in bacteria or the interspacer region in fungi).71”
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    • cites [71] Pérez‐Cobas AE, Gomez‐Valero L, Buchrieser C. Metagenomic approaches in microbial ecology: an update on whole‐genome and marker gene sequencing analyses. Microb Genomics. 2020; 6(8): mgen000409. 10.1099/mgen.0.000409 PMC7641418 32706331 source

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    Premisecitation

    Short-read technology provides abundant sequencing data that is less error prone than long-read technology; however, it can be difficult to assemble complete genomes using short read-lengths due to limitations in distinguishing repetitive elements.

    “short‐read technology provides abundant sequencing data that is less error prone than long‐read technology; however, it can be difficult to assemble complete genomes using short read‐lengths due to limitations in the technology to distinguish repetitive elements.”
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    • cites [82] Pearman WS, Freed NE, Silander OK. Testing the advantages and disadvantages of short‐and long‐read eukaryotic metagenomics using simulated reads. BMC Bioinformatics. 2020; 21: 1‐ 15. 32471343 PMC7257156 source

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    Metabolite production is influenced by the availability of energy sources, environmental stressors, and competition among microbes within a system.

    “Metabolite production is influenced by the availability of energy sources, environmental stressors, and competition among microbes within a system.5”
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    • cites [5] Vernocchi P, Del Chierico F, Putignani L. Gut microbiota profiling: metabolomics based approach to unravel compounds affecting human health. Front Microbiol. 2016; 7: 1144. 27507964 PMC4960240 source

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    Shotgun metagenomics employs random fragmentation and adapter ligation to sequence in an unbiased manner all extracted DNA, enabling more in-depth analyses of the pan-genomic gene content in microbiomes.

    “This approach employs random fragmentation and adapter ligation sequence in an unbiased manner all extracted DNA, enabling more in‐depth analyses of the pan‐genomic gene content in microbiomes.3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Bikel S, Valdez‐Lara A, Cornejo‐Granados F, et al. Combining metagenomics, metatranscriptomics and viromics to explore novel microbial interactions: towards a systems‐level understanding of human microbiome. Comput Struct Biotechnol J. 2015; 13: 390‐ 401. 26137199 PMC4484546 source

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    Long-read technology provides more read-length but at the cost of higher error rates.

    “By contrast, long‐read technology provides more read‐length but at the cost of higher error rates.82”
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    • cites [82] Pearman WS, Freed NE, Silander OK. Testing the advantages and disadvantages of short‐and long‐read eukaryotic metagenomics using simulated reads. BMC Bioinformatics. 2020; 21: 1‐ 15. 32471343 PMC7257156 source

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    Metatranscriptomics, or sequencing of mRNA in a sample, provides a snapshot of transcriptionally active microbes.

    “Metatranscriptomics, or sequencing of mRNA in a sample, provides a snapshot of transcriptionally active microbes.89”
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    • cites [89] Nguyen T, Sedghi L, Ganther S, Malone E, Kamarajan P, Kapila YL. Host‐microbe interactions: profiles in the transcriptome, the proteome, and the metabolome. Periodontol 2000. 2020; 82(1): 115‐ 128. 10.1111/prd.12316 31850641 PMC7968888 source

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    Premisecitation

    Functions of immune networks within oral mucosa reflect the site-specific challenges faced within the oral cavity; they contribute to homeostasis in response to masticatory forces and trigger immune responses to the development of pathologic microbial communities.

    “In line with the role of oral mucosa as a physiological barrier, the functions of immune networks within this mucosa reflect the site‐specific challenges faced within the oral cavity. For example, they contribute to homeostasis in response to masticatory forces and trigger immune responses to the development of pathologic microbial communities.52, 53”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [52] Dutzan N, Kajikawa T, Abusleme L, et al. A dysbiotic microbiome triggers T H 17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018; 10(463): eaat0797. 10.1126/scitranslmed.aat0797 30333238 PMC6330016 source

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    • cites [53] Dutzan N, Abusleme L, Bridgeman H, et al. On‐going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity. 2017; 46(1): 133‐ 147. 10.1016/j.immuni.2016.12.010 28087239 PMC5263257 source

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    Premisecitation

    Firmicutes, Bacteroides, and Actinobacteria were found to be most abundant, respectively, in babies delivered vaginally, while Bacteroides, Proteobacteria, and Firmicutes were most abundant in babies delivered by Cesarean section.

    “Firmicutes, Bacteroides, and Actinobacteria were found to be most abundant, respectively, in babies delivered vaginally, while Bacteroides, Proteobacteria, and Firmicutes were most abundant in babies delivered by Cesarean section.”
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    • cites [121] Li H, Wang J, Wu L, et al. The impacts of delivery mode on infant’s oral microflora. Sci Rep. 2018; 8(1): 1‐ 6. 30093722 PMC6085361

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    Premisecitation

    The infant mouth becomes colonized by early oral colonizers associated with the infant's mode of delivery, demonstrated by finding distinct differences in the bacterial phyla predominant in the oral cavities of babies delivered vaginally compared with those delivered by Cesarean section.

    “The infant mouth becomes colonized by early oral colonizers associated with the infant's mode of delivery,121 demonstrated by finding distinct differences in the bacterial phyla predominant in the oral cavities of babies delivered vaginally compared with those delivered by Cesarean section.121”
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    • cites [121] Li H, Wang J, Wu L, et al. The impacts of delivery mode on infant’s oral microflora. Sci Rep. 2018; 8(1): 1‐ 6. 30093722 PMC6085361

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    Premisecitation

    Streptococci are capable of adhering to epithelial cells and are a dominant bacterial group in breast milk.

    “Streptococci are capable of adhering to epithelial cells and are a dominant bacterial group in breast milk.144”
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    • cites [144] Boix‐Amorós A, Collado MC, Mira A. Relationship between milk microbiota, bacterial load, macronutrients, and human cells during lactation. Front Microbiol. 2016; 7: 492. 10.3389/fmicb.2016.00492 27148183 PMC4837678 source

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    Premisecitation

    Strong host genetic factors existed for several taxa and microbial metabolic functions relevant to caries development in the younger cohort, while strong host genetic factors on serum antibody levels against known periodontal pathogens existed in the older age group.

    “Notably, strong host genetic factors existed for several taxa and microbial metabolic functions relevant to caries development in the younger cohort, while strong host genetic factors on serum antibody levels against known periodontal pathogens existed in the older age group.108”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Esberg A, Haworth S, Kuja‐Halkola R, Magnusson PKE, Johansson I. Heritability of oral microbiota and immune responses to oral bacteria. Microorganisms. 2020; 8(8): 1126. 10.3390/microorganisms8081126 PMC7464143 32726935 source

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  • May combine two claims.

    Premisecitation

    As children age, their oral microbiomes tend to stabilize, a feature attributed to the establishment of independent oral-hygiene maintenance habits, acquisition of permanent dentition, and consumption of an adult diet with more-or-less defined dietary patterns.

    “As children age, their oral microbiomes tend to stabilize, a feature attributed to the establishment of independent oral‐hygiene maintenance habits, acquisition of permanent dentition, and consumption of an adult diet with more‐or‐less defined dietary patterns.135”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [135] Gomez A, Nelson KE. The oral microbiome of children: development, disease, and implications beyond oral health. Microb Ecol. 2017; 73(2): 492‐ 503. 27628595 PMC5274568 source

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  • May combine two claims.

    Premisecitation

    Streptococcus salivarius demonstrates the highest relative abundance among newborns and shows a steady decrease after 3 months of age.

    “Streptococcus salivarius demonstrates the highest relative abundance among newborns and shows a steady decrease after 3 months of age.119”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [119] Nelson‐Filho P, Borba IG, Mesquita KSF, et al. Dynamics of microbial colonization of the oral cavity in newborns. Braz Dent J. 2013; 24(4): 415‐ 419. 10.1590/0103-6440201302266 24173267 source

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  • May combine two claims.

    Premisecitation

    Vast differences in relative abundance at the genus level have been observed for most phyla, with the most marked increases being observed for Lactobacillus species in children delivered vaginally and for Petrimonas species in children delivered by Cesarean section.

    “Regarding mode of delivery, vast differences in relative abundance at the genus level have been observed for most phyla, with the most marked increases being observed for Lactobacillus species in children delivered vaginally and for Petrimonas species in children delivered by Cesarean section.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [121] Li H, Wang J, Wu L, et al. The impacts of delivery mode on infant’s oral microflora. Sci Rep. 2018; 8(1): 1‐ 6. 30093722 PMC6085361

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  • May combine two claims.

    Premisecitation

    In a study of 12 mother-neonate pairs, the microbiota of the neonatal oral cavity displayed clear associations with that of the placenta and was not significantly altered by the birth canal or maternal microbiotas, suggesting that the neonatal microbiota may have a prenatal origin.

    “Interestingly, in a study of 12 mother‐neonate pairs, it was found that the microbiota of the neonatal oral cavity displayed clear associations with that of the placenta and was not significantly altered by the birth canal or maternal microbiotas, suggesting that the neonatal microbiota may have a prenatal origin.112”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [112] Tuominen H, Collado MC, Rautava J, Syrjänen S, Rautava S. Composition and maternal origin of the neonatal oral cavity microbiota. J. Oral Microbiol. 2019; 11(1): 1663084. 10.1080/20002297.2019.1663084 31528268 PMC6735328 source

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  • May combine two claims.

    Premisecitation

    Additional early colonizers, such as Gemella, Rothia, Granulicatella, and Haemophilus, are present at 3-6 months of age and increase in abundance with time.

    “Additional early colonizers, such as Gemella, Rothia, Granulicatella, and Haemophilus, present at 3‐6 months of age and increase in abundance with time.141, 142”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [141] Xiao J, Fiscella KA, Gill SR. Oral microbiome: possible harbinger for children’s health. Int J Oral Sci. 2020; 12(1): 1‐ 13. 10.1038/s41368-020-0082-x 32350240 PMC7190716 source

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    • cites [142] Dzidic M, Collado MC, Abrahamsson T, et al. Oral microbiome development during childhood: an ecological succession influenced by postnatal factors and associated with tooth decay. ISME J. 2018; 12(9): 2292‐ 2306. 10.1038/s41396-018-0204-z 29899505 PMC6092374 source

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  • May combine two claims.

    Premisecitation

    Studies investigating the placental microbiome to understand its role in preterm pregnancies have identified bacteria associated with periodontal disease, suggesting a relationship between the oral and placental microbiomes.

    “Studies investigating the placental microbiome to understand its role in preterm pregnancies have identified bacteria associated with periodontal disease, suggesting a relationship between the oral and placental microbiomes.113, 114, 115, 116”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [113] Cobb CM, Kelly PJ, Williams KB, Babbar S, Angolkar M, Derman RJ. The oral microbiome and adverse pregnancy outcomes. Int J Womens Health. 2017; 9: 551‐ 559. 10.2147/IJWH.S142730 28848365 PMC5557618 source

      Not checked in the free run.

    • cites [114] Han YW. Oral health and adverse pregnancy outcomes – what’s next? J Dent Res. 2011; 90(3): 289‐ 293. 10.1177/0022034510381905 21041548 PMC3144105 source

      Not checked in the free run.

    • cites [115] Vander Haar EL, So J, Gyamfi‐Bannerman C, Han YW. Fusobacterium nucleatum and adverse pregnancy outcomes: epidemiological and mechanistic evidence. Anaerobe. 2018; 50: 55‐ 59. 10.1016/j.anaerobe.2018.01.008 29409815 PMC6750227 source

      Not checked in the free run.

    • cites [116] Gomez‐Arango LF, Barrett HL, McIntyre HD, et al. Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women. Sci Rep. 2017; 7: 2860. 10.1038/s41598-017-03066-4 28588199 PMC5460277 source

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  • May combine two claims.

    Premisenone given

    The eruption of teeth leads to divergence of the infant oral microbiota from the maternal microbiota, and such changes persist among mixed and permanent dentition states.

    “The eruption of teeth leads to divergence of the infant oral microbiota from the maternal microbiota, and such changes persist among mixed and permanent dentition states.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The composition of one's oral microbiome locally impacts oral health and may also affect systemic health throughout life.

    “Not only does the composition of one's oral microbiome locally impact oral health, it may also affect systemic health throughout life.38”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Sampaio‐Maia B, Caldas I, Pereira M, Perez‐Mongiovi D, Araujo R. The oral microbiome in health and its implication in oral and systemic diseases. Adv Appl Microbiol. 2016; 97: 171‐ 210. 27926431 source

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  • May combine two claims.

    Premisecitation

    Lactococcus lactis produces nisin, a bacteriocin that has been shown to reduce oral tumorigenesis and extend the life span of mice with tumors.

    “Lactococcus lactis, a commensal of the oral microbiota, produces nisin, a bacteriocin that has been shown to reduce oral tumorigenesis and extend the life span of mice with tumors.165, 166”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [165] Shin JM, Gwak JW, Kamarajan P, Fenno JC, Rickard AH, Kapila YL. Biomedical applications of nisin. J Appl Microbiol. 2016; 120(6): 1449‐ 1465. 10.1111/jam.13033 26678028 PMC4866897 source

      Not checked in the free run.

    • cites [166] Kamarajan P, Hayami T, Matte B, et al. Nisin ZP, a bacteriocin and food preservative, inhibits head and neck cancer tumorigenesis and prolongs survival. PLoS One. 2015; 10(7): e0131008. 10.1371/journal.pone.0131008 26132406 PMC4489501 source

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  • May combine two claims.

    Premisecitation

    Clinical isolates from individuals with good oral health status contained strains of Streptococcus, Actinomyces, and Bifidobacterium, all of which were shown to inhibit growth of P gingivalis.

    “Moreover, clinical isolates from individuals with good oral health status contained strains of Streptococcus, Actinomyces, and Bifidobacterium, all of which were shown to inhibit growth of P gingivalis.164”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [164] van Essche M, Loozen G, Godts C, et al. Bacterial antagonism against periodontopathogens. J Periodontol. 2013; 84(6): 801‐ 811. 10.1902/jop.2012.120261 22897652 source

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  • May combine two claims.

    Premisecitation

    Nearly 25% of ingested nitrate is transported via the enterosalivary circuit to the oral cavity, where oral microbes reduce nitrate to nitrite, which is taken into the bloodstream during digestion and converted to nitric oxide.

    “Nearly 25% of ingested nitrate is transported, via the enterosalivary circuit, to the oral cavity: here, oral microbes reduce nitrate to nitrite, which is taken into the bloodstream during digestion and converted to nitric oxide.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] Wade WG. The oral microbiome in health and disease. Pharmacol Res. 2013; 69(1): 137‐ 143. 10.1016/j.phrs.2012.11.006 23201354 source

      Not checked in the free run.

    • cites [168] Govoni M, Jansson EÅ, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide. 2008; 19(4): 333‐ 337. 10.1016/j.niox.2008.08.003 18793740 source

      Not checked in the free run.

    • cites [170] Bondonno CP, Liu AH, Croft KD, et al. Antibacterial Mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men and women. Am J Hypertens. 2015; 28(5): 572‐ 575. 25359409 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    After the colon, the oral microbiome represents the second most diverse microbiota in the human host, with over 700 bacterial species presently identified.

    “After the colon, the oral microbiome represents the second most diverse microbiota in the human host, with over 700 bacterial species presently identified.35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Deo PN, Deshmukh R. Oral microbiome: unveiling the fundamentals. J Oral Maxillofac Pathol. 2019; 23(1): 122. PMC6503789 31110428 source

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  • May combine two claims.

    Premisecitation

    Among infants, phylogenetic divergences across individuals are observed prior to eruption of deciduous teeth, but functional signatures remain conserved.

    “Among infants, phylogenetic divergences across individuals are observed prior to eruption of deciduous teeth143; however, functional signatures remain conserved.143”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [143] Mason MR, Chambers S, Dabdoub SM, Thikkurissy S, Kumar PS. Characterizing oral microbial communities across dentition states and colonization niches. Microbiome. 2018; 6(1): 1‐ 10. 10.1186/s40168-018-0443-2 29631628 PMC5891995 source

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  • May combine two claims.

    Premisecitation

    Other core members with greater than 1% abundance across at least 80% of samples from one or more sites included Pasteurellaceae, Gemella, Veillonella, Prevotella, Fusobacterium, Porphyromonas, Neisseria, Capnocytophaga, Corynebacterium, Actinomyces, Lactobacillales, and Lachnospiraceae.

    “Other core members with greater than 1% abundance across at least 80% of samples from 1 or more sites, included those from the family Pasteurellaceae, those from the genera Gemella, Veillonella, Prevotella, Fusobacterium, Porphyromonas, Neisseria, Capnocytophaga, Corynebacterium, and Actinomyces, and those from the orders Lactobacillales and Lachnospiraceae.160”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [160] Dewhirst FE, Chen T, Izard J, et al. The human oral microbiome. J. Bacteriol. 2010; 192(19): 5002‐ 5017. 20656903 PMC2944498 source

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  • May combine two claims.

    Premisecitation

    Nisin was demonstrated in vitro to mitigate pathogen-mediated oral tumorigenesis, cancer cell migration, and cell invasion of oral squamous cell carcinoma, suggesting an anti-cancer role for commensal species.

    “In addition, nisin was recently demonstrated in vitro to mitigate pathogen‐mediated oral tumorigenesis, cancer cell migration, and cell invasion of oral squamous cell carcinoma in vitro, thus suggesting an anti‐cancer role for commensal species.167”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [167] Kamarajan P, Ateia I, Shin JM, et al. Periodontal pathogens promote cancer aggressivity via tlr/myd88 triggered activation of integrin/FAK signaling that is therapeutically reversible by a probiotic bacteriocin. PLOS Pathog. 2020; 16(10): e1008881. 10.1371/journal.ppat.1008881 33002094 PMC7529280 source

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  • May combine two claims.

    Interpretationreasoning

    The commensal oral microbiome is important in maintaining oral health and promoting systemic health.

    “Such findings demonstrate the importance of the commensal oral microbiome in maintaining oral health and promoting systemic health.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Carious lesions, if left untreated, may lead to more advanced oral pathologies, such as abscess formation or pulpal involvement.

    “Carious lesions, if left untreated, may lead to more advanced oral pathologies, such as abscess formation or pulpal involvement.190”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [190] Monse B, Heinrich‐Weltzien R, Benzian H, Holmgren C, Helderman WVP. PUFA – An index of clinical consequences of untreated dental caries. Community Dent Oral Epidemiol. 2010; 38(1): 77‐ 82. 10.1111/j.1600-0528.2009.00514.x 20002630 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The prevalence of untreated caries decreased from 18.6% for youths living below the federal poverty line to 7% among youths in families with incomes 300% above the federal poverty line.

    “Moreover, the prevalence of untreated caries decreased from 18.6% for youths living below the federal poverty line to 7% among youths in families with incomes 300% above the federal poverty line.191”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [191] Eleanor F, Joseph A. Prevalence of Total and Untreated Dental Caries Among Youth: United States, 2015–2016, http://pubmed.ncbi.nlm.nih.gov/29717975/. Accessed December 9, 2020

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  • May combine two claims.

    Premisecitation

    Key species in oral biofilm are recognized as etiological agents in the development of periodontal disease, including the red complex bacteria T forsythia, Treponema denticola, and P gingivalis, which drive periodontal disease pathogenesis by orchestrating restructure of the microbiota and promoting inflammation.

    “Key species in oral biofilm are recognized as etiological agents in the development of periodontal disease: these species include the red complex bacteria—T forsythia, Treponema denticola, and P gingivalis—that exhibit the capacity to drive the processes involved in periodontal disease pathogenesis by orchestrating restructure of the microbiota and promoting inflammation.178”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [178] Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol. 2012; 27(6): 409‐ 419. 23134607 PMC3653317 source

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  • May combine two claims.

    Premisecitation

    While the inflammation characteristics of gingivitis are mostly reversible, periodontitis results in long-term, irreversible damage to the periodontal tissues and alveolar bone that manifests as tissue detachment from the tooth, formation of a pocket wherein pathogenic bacteria can proliferate further, and eventual tooth loss in advanced stages of the disease.

    “While the inflammation characteristics of gingivitis are mostly reversible, periodontitis results in long‐term, irreversible damage to the periodontal tissues and alveolar bone that manifests as tissue detachment from the tooth, formation of a pocket wherein pathogenic bacteria can proliferate further, and eventual tooth loss in advanced stages of the disease.192, 193, 194, 195”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [192] Koenig JE, Spor A, Scalfone N, et al. succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci USA 2011; 108(Supp. 1): 4578‐ 4585. 20668239 PMC3063592 source

      Not checked in the free run.

    • cites [193] Li M, Wang M, Donovan SM. Early development of the gut microbiome and immune‐mediated childhood disorders. Sem Reprod Med. 2014; 32(01): 74‐ 086. 10.1055/s-0033-1361825 24390924 source

      Not checked in the free run.

    • cites [194] Wu R‐Q, Zhang D‐F, Tu E, Chen Q‐M, Chen W. The mucosal immune system in the oral cavity—an orchestra of t cell diversity. Int J Oral Sci. 2014; 6(3): 125‐ 132. 25105816 PMC4170154 source

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    • cites [195] Yu JC, Khodadadi H, Malik A, et al. Innate immunity of neonates and infants. Front Immunol. 2018; 9: 1759. 30105028 PMC6077196 source

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  • May combine two claims.

    Premisecitation

    Dysbiosis is prompted by various factors, including host diet, inflammatory responses, systemic disruptions, and habits such as alcohol intake, smoking tobacco and consuming alcohol.

    “Such dysbiosis is prompted by various factors, including host diet, inflammatory responses, systemic disruptions, and habits such as alcohol intake, smoking tobacco and consuming alcohol.50, 180, 181, 182, 183, 184, 185, 186”
    Quote in the paperNot a substantial claim0 of 8 sources checked
    • cites [50] Xiao E, Mattos M, Vieira GHA, et al. Diabetes enhances IL‐17 expression and alters the oral microbiome to increase its pathogenicity. Cell Host Microbe. 2017; 22(1): 120‐ 128.e4. 10.1016/j.chom.2017.06.014 28704648 PMC5701758 source

      Not checked in the free run.

    • cites [180] Wang Y, Wang S, Wu C, et al. Oral microbiome alterations associated with early childhood caries highlight the importance of carbohydrate metabolic activities. MSystems. 2019; 4(6): e00450‐19. 31690590 PMC6832018 source

      Not checked in the free run.

    • cites [181] Klein MI, DeBaz L, Agidi S, et al. Dynamics of Streptococcus mutans transcriptome in response to starch and sucrose during biofilm development. PLoS One. 2010; 5(10): e13478. 10.1371/journal.pone.0013478 20976057 PMC2957427 source

      Not checked in the free run.

    • cites [182] Chapple ILC. Potential mechanisms underpinning the nutritional modulation of periodontal inflammation. J Am Dent Assoc. 2009; 140(2): 178‐ 184. 10.14219/jada.archive.2009.0131 19188414 source

      Not checked in the free run.

    • cites [183] Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000. 2014; 64(1): 57‐ 80. 10.1111/prd.12002 24320956 PMC4500791 source

      Not checked in the free run.

    • cites [184] De Pablo P, Dietrich T, McAlindon TE. Association of Periodontal disease and tooth loss with rheumatoid arthritis in the US population. J Rheumatol. 2008; 35(1): 70‐ 76. 18050377

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    • cites [185] Wu J, Peters BA, Dominianni C, et al. Cigarette smoking and the oral microbiome in a large study of american adults. ISME J. 2016; 10(10): 2435‐ 2446. 10.1038/ismej.2016.37 27015003 PMC5030690 source

      Not checked in the free run.

    • cites [186] Pitiphat W, Merchant AT, Rimm EB, Joshipura KJ. Alcohol consumption increases periodontitis risk. J Dent Res. 2003; 82(7): 509‐ 513. 10.1177/154405910308200704 12821709 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Untreated carious lesions among adolescents comprise nearly 15% of the total cases of caries among adolescents aged 12-19 years, with untreated carious lesions primarily occurring in non-Hispanic black youth (17.1%), followed by Hispanic (13.5%), non-Hispanic white (11.7%), and non-Hispanic Asian (10.5%) youth.

    “Fleming and Afful found that untreated carious lesions among adolescents comprise nearly 15% of the total cases of caries among adolescents aged 12‐19 years, with untreated carious lesions primarily occurring in non‐Hispanic black youth (17.1%), followed by Hispanic (13.5%), non‐Hispanic white (11.7%), and non‐Hispanic Asian (10.5%) youth.191”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [191] Eleanor F, Joseph A. Prevalence of Total and Untreated Dental Caries Among Youth: United States, 2015–2016, http://pubmed.ncbi.nlm.nih.gov/29717975/. Accessed December 9, 2020

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Three primary mechanisms linking oral infection to systemic pathology have been identified: spread of infection from the oral cavity as a result of transient bacteremia; circulation of microbial toxins; and systemic inflammation caused by adverse immunologic responses to oral microbes.

    “Three primary mechanisms linking oral infection to systemic pathology have been identified: spread of infection from the oral cavity as a result of transient bacteremia; circulation of microbial toxins; and systemic inflammation caused by adverse immunologic responses to oral microbes.196”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [196] Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases caused by oral infection. Clin Microbiol Rev. 2000; 13(4): 547‐ 558. 11023956 PMC88948 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most oral bacteria are not well adapted to survive in a healthy lower gastrointestinal tract; however, increased levels of oral-associated microbes are found in the gut of patients with inflammatory bowel disease, HIV, liver cirrhosis, and colon cancer.

    “Most oral bacteria are not well adapted to survive in a healthy lower gastrointestinal tract; however, increased levels of oral‐associated microbes are found in the gut of patients with inflammatory bowel disease, HIV, liver cirrhosis, and colon cancer.39, 41”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Atarashi K, Suda W, Luo C, et al. Ectopic colonization of oral bacteria in the intestine drives Th1 cell induction and inflammation. Science. 2017; 358(6361): 359‐ 365. 29051379 PMC5682622 source

      Not checked in the free run.

    • cites [41] d’Ettorre G, Oliva A, DeAngelis M, Vullo VRE. Ectopic colonization of oral bacteria in the intestine drives Th1 cell induction and. Inflammation. Science. 2019; 358: 359‐ 365. PMC5682622 29051379

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  • May combine two claims.

    Premisecitation

    Periodontal disease is caused by dysbiosis of subgingival microbial communities that adversely affects the host immune system such that it creates and maintains unmitigated inflammation in gingival and periodontal tissues, thus preventing immune subversion and tissue recovery.

    “Periodontal disease is caused by dysbiosis of subgingival microbial communities that adversely affects the host immune system such that it creates and maintains unmitigated inflammation in gingival and periodontal tissues, thus preventing immune subversion and tissue recovery.10”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015; 15(1): 30‐ 44. 10.1038/nri3785 25534621 PMC4276050 source

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  • May combine two claims.

    Interpretationcitation

    In addition to causing local periodontal disease, oral infection has implications in systemic disease.

    “In addition to causing local (periodontal) disease, oral infection has implications in systemic disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Between 0.75 and 1.5 L of saliva are produced per day by the oral cavity and the majority is swallowed either alone or with food or drink.

    “Between 0.75 and 1.5 L of saliva are produced per day by the oral cavity and the majority is swallowed either alone or with food or drink.198”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [198] Dawes C. Salivary flow patterns and the health of hard and soft oral tissues. J. Am Dent Assoc. 2008; 139: 18S‐ 24S. 18460676 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Saliva contains 10^9 bacteria per milliliter, with the bacteria present in saliva being shed from the tongue, cheeks, and dental and gingival plaque.

    “Saliva contains 109 bacteria per milliliter, with the bacteria present in saliva being shed from the tongue, cheeks, and dental and gingival plaque.197”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [197] Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol. 1996; 4(11): 430‐ 435. 8950812 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Untreated dental caries is the most common reason for hospitalization of youth.

    “Untreated dental caries is the most common reason for hospitalization of youth.155”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [155] Acharya A, Khan S, Hoang H, Bettiol S, Goldberg L, Crocombe L. Dental conditions associated with preventable hospital admissions in Australia: a systematic literature review. BMC Health Serv. Res. 2018; 18: 921. 10.1186/s12913-018-3733-2 30509254 PMC6278106 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These diseases are often associated with a perturbed gut microbiota, suggesting an increased ability of oral microbes to colonize ectopically in the context of immune dysregulation.

    “These diseases are often associated with a perturbed gut microbiota, suggesting an increased ability of oral microbes to colonize ectopically in the context of immune dysregulation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Porphyromonas gingivalis expresses peptidyl arginine deaminase, which citrullinates gingival proteins and bacterial peptides, and also undergoes autocitrullination.

    “Porphyromonas gingivalis also expresses peptidyl arginine deaminase, which citrullinates gingival proteins and bacterial peptides, and also undergoes autocitrullination.208”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [208] Bingham CO, Moni M. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions. Curr Opin Rheumatol. 2013; 25(3): 345‐ 353. 10.1097/BOR.0b013e32835fb8ec 23455329 PMC4495574 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A diagnosis of Alzheimer's disease correlates with the gingipain load in the brain and also with other P gingivalis-specific virulence factors, including P gingivalis lipopolysaccharide.

    “A diagnosis of Alzheimer's disease correlates with the gingipain load in the brain and also with other P gingivalis‐specific virulence factors, including P gingivalis lipopolyaccharide.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [213] Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small‐molecule inhibitors. Sci Adv. 2019; 5(1): eaau3333. 30746447 PMC6357742 source

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  • May combine two claims.

    Premisecitation

    Gingipains cleave tau protein and contribute to tau tangle formation resulting disease.

    “It has now been demonstrated that gingipains cleave tau protein and contribute to tau tangle formation resulting disease.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [213] Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small‐molecule inhibitors. Sci Adv. 2019; 5(1): eaau3333. 30746447 PMC6357742 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies in mice have shown that oral P gingivalis consistently invades the brain in a gingipain-assisted manner, and that injection of gingipains into the brain increases neuronal degeneration to a level higher than that found in controls.

    “Studies in mice have shown that oral P gingivalis consistently invades the brain in a gingipain‐assisted manner, and that injection of gingipains into the brain increases neuronal degeneration to a level higher than that found in controls.213”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [213] Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small‐molecule inhibitors. Sci Adv. 2019; 5(1): eaau3333. 30746447 PMC6357742 source

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models, such as germ-free mice, about oral bacteria and systemic inflammation can be extrapolated to human disease.

  • May combine two claims.

    Premisecitation

    When rheumatoid arthritis is treated, the oral microbiome is partially restored, and vice versa.

    “When rheumatoid arthritis is treated, the oral microbiome is partially restored, and vice versa.207, 208”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [207] Kobayashi T, Yokoyama T, Ishida K, Abe A, Yamamoto K, Yoshie H. Serum cytokine and periodontal profiles in relation to disease activity of rheumatoid arthritis in Japanese adults. J Periodontol. 2010; 81(5): 650‐ 657. 10.1902/jop.2010.090688 20429644 source

      Not checked in the free run.

    • cites [208] Bingham CO, Moni M. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions. Curr Opin Rheumatol. 2013; 25(3): 345‐ 353. 10.1097/BOR.0b013e32835fb8ec 23455329 PMC4495574 source

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  • May combine two claims.

    Premisecitation

    T denticola, P gingivalis, and F nucleatum enhance cell migration, invasiveness, stemness, and oral tumorigenesis of oral squamous cell carcinomas but have little effect on cell proliferation and apoptosis.

    “Their findings demonstrate that T denticola, P gingivalis, and F nucleatum enhance cell migration, invasiveness, stemness, and oral tumorigenesis of oral squamous cell carcinomas but have little effect on cell proliferation and apoptosis.167”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [167] Kamarajan P, Ateia I, Shin JM, et al. Periodontal pathogens promote cancer aggressivity via tlr/myd88 triggered activation of integrin/FAK signaling that is therapeutically reversible by a probiotic bacteriocin. PLOS Pathog. 2020; 16(10): e1008881. 10.1371/journal.ppat.1008881 33002094 PMC7529280 source

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    Premisecitation

    Such pro-inflammatory molecules can directly access the circulatory system and induce systemic effects, such as coagulation and thrombosis, platelet aggregation and adhesion, and accumulation of cholesterol deposits.

    “Such pro‐inflammatory molecules can directly access the circularity (cardiovascular) system and induce systemic effects, such as coagulation and thrombosis, platelet aggregation and adhesion, and accumulation of cholesterol deposits.196”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [196] Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases caused by oral infection. Clin Microbiol Rev. 2000; 13(4): 547‐ 558. 11023956 PMC88948 source

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  • May combine two claims.

    Premisereasoning

    Subgingival biofilms have a large bacterial load and, because of their close proximity to deeper periodontal tissues, may serve as reservoirs of lipopolysaccharide and gram-negative pathogens for systemic circulation.

    “Subgingival biofilms have a large bacterial load and, because of their close proximity to deeper periodontal tissues, may serve as reservoirs of lipopolysaccharide and gram‐negative pathogens for systemic circulation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Rheumatoid arthritis is a chronic autoimmune disease characterized by synovial inflammation that can result in damage to articular cartilage and bone.

    “Rheumatoid arthritis is a chronic autoimmune disease characterized by synovial inflammation that can result in damage to articular cartilage and bone.205”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [205] McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011; 365(23): 2205‐ 2219. 22150039 source

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  • May combine two claims.

    Premisecitation

    Studies have revealed a link between rheumatoid arthritis and dysbiosis of the gut and oral cavity microbiomes, and a long-term correlation between periodontal disease and rheumatoid arthritis exists.

    “Studies have revealed a link between rheumatoid arthritis and dysbiosis of the gut and oral cavity microbiomes, and a long‐term correlation between periodontal disease and rheumatoid arthritis exists.206”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [206] De Pablo P, Dietrich T, McAlindon TE. Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population. J Rheumatol. 2008; 35(1): 70‐ 76. 18050377

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  • May combine two claims.

    Premisecitation

    Lipopolysaccharide induces secretion of inflammatory factors that promote platelet aggregation and adhesion, formation of lipid foam cells, and accumulation of cholesterol deposits.

    “Moreover, lipopolysaccharide induces secretion of inflammatory factors that promote platelet aggregation and adhesion, formation of lipid foam cells, and accumulation of cholesterol deposits.196”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [196] Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases caused by oral infection. Clin Microbiol Rev. 2000; 13(4): 547‐ 558. 11023956 PMC88948 source

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  • May combine two claims.

    Premisecitation

    Periodontal disease shares many associative and causative links with systemic disease, and it increases susceptibility to systemic diseases via shared risk factors, such as by harboring pathogenic gram-negative anaerobes in subgingival biofilms, and by fashioning the periodontium as a reservoir for pro-inflammatory mediators.

    “Periodontal disease shares many associative and causative links with systemic disease, and it increases susceptibility to systemic diseases via shared risk factors, such as by harboring pathogenic gram‐negative anaerobes in subgingival biofilms, and by fashioning the periodontium as a reservoir for pro‐inflammatory mediators.199”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [199] Page RC. The pathobiology of periodontal diseases may affect systemic diseases: inversion of a paradigm. Ann Periodontol. 1998; 3(1): 108‐ 120. 10.1902/annals.1998.3.1.108 9722695 source

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  • May combine two claims.

    Premisenone given

    Chronic psychological stress is classified as a risk indicator for periodontal disease and may serve as an early sign of increased risk for development of periodontal disease.

    “Chronic psychological stress is also classified as a risk indicator for periodontal disease and may serve as an early sign of increased risk for development of periodontal disease.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Traditional models of microbial biofilm succession follow a sequential process in which the initial attachment of primary colonizers, namely Streptococcus, Actinomyces, Gemella, Veillonella, Rothia, and Neisseria species, bind to dental pellicle and facilitate subsequent colonization by F nucleatum, which functions as a bridging species between early and late colonizers.

    “Traditional models of microbial biofilm succession follow a sequential process in which the initial attachment of primary colonizers, namely Streptococcus, Actinomyces, Gemella, Veillonella, Rothia, and Neisseria species, bind to dental pellicle and facilitate subsequent colonization by F nucleatum, which functions as a bridging species between early and late colonizers.235”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [235] Jakubovics NS. Intermicrobial interactions as a driver for community composition and stratification of oral biofilms. J Mol Biol. 2015; 427(23): 3662‐ 3675. 10.1016/j.jmb.2015.09.022 26519790 source

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  • May combine two claims.

    Premisecitation

    While traditional models recognize Fusobacterium as critical for connecting early and late biofilm successors, findings from this study instead found Corynebacterium as the cornerstone of biofilm development.

    “While traditional models recognize Fusobacterium as critical for connecting early and late biofilm successors, findings from this study instead found Cornybacterium as the cornerstone of biofilm development.61, 236”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [61] Mark Welch JL, Rossetti BJ, Rieken CW, Dewhirst FE, Borisy GG. Biogeography of a human oral microbiome at the micron scale. Proc Natl Acad Sci USA. 2016; 113(6): E791‐ E800. 10.1073/pnas.1522149113 26811460 PMC4760785 source

      Not checked in the free run.

    • cites [236] Kolenbrander PE, Palmer RJ, Rickard AH, Jakubovics NS, Chalmers NI, Diaz PI. Bacterial interactions and successions during plaque development. Periodontol 2000. 2006; 42(1): 47‐ 79. 10.1111/j.1600-0757.2006.00187.x 16930306 source

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  • May combine two claims.

    Premisecitation

    The stress hormone cortisol has been shown to directly induce shifts in the composition of the oral microbial community and in its gene expression profiles in vitro, which reproduces results found for the gene expression profiles of the oral microbial community in periodontal disease and during its progression.

    “Moreover, the stress hormone, cortisol, has been shown to directly induce shifts in the composition of the oral microbial community and in its gene expression profiles in vitro, which reproduces results found for the gene expression profiles of the oral microbial community in periodontal disease and during its progression.94”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] Duran‐Pinedo AE, Solbiati J, Frias‐Lopez J. The effect of the stress hormone cortisol on the metatranscriptome of the oral microbiome. NPJ Biofilms Microbiomes. 2018; 4(1): 1‐ 4. 10.1038/s41522-018-0068-z 30345066 PMC6194028 source

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  • May combine two claims.

    Premisecitation

    Emerging evidence suggests that chronic stress and related diseases, such as depression and anxiety, may be significant factors contributing to the development of oral dysbiosis, progression of periodontal/peri-implant disease, and inconsistent wound healing following periodontal therapy.

    “Emerging evidence suggests that chronic stress and related diseases, such as depression and anxiety, may be significant factors contributing to the development of oral dysbiosis, progression of periodontal/peri‐implant disease, and inconsistent wound healing following periodontal therapy.125, 224, 225, 226”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [125] Castro MML, de Ferreira RO, Fagundes NCF, et al. Association between psychological stress and periodontitis: a systematic review. Eur J Dent. 2020; 14(1): 171‐ 179. 10.1055/s-0039-1693507 32069501 PMC7069755 source

      Not checked in the free run.

    • cites [224] Decker A, Askar H, Tattan M, Taichman R, Wang H‐L. The assessment of stress, depression, and inflammation as a collective risk factor for periodontal diseases: a systematic review. Clin Oral Investig. 2020; 24(1): 1‐ 12. 10.1007/s00784-019-03089-3 PMC6980776 31677052 source

      Not checked in the free run.

    • cites [225] Gomaa N, Glogauer M, Nicolau B, et al. Stressed‐out oral immunity: a gateway from socioeconomic adversity to periodontal disease. Psychosom Med. 2020; 82(2): 126‐ 137. 10.1097/PSY.0000000000000774 31860530 source

      Not checked in the free run.

    • cites [226] Spector AM, Postolache TT, Akram F, Scott AJ, Wadhawan A, Reynolds MA. Psychological stress: a predisposing and exacerbating factor in periodontitis. Curr Oral Health Rep. 2020; 7(3): 208‐ 215. 10.1007/s40496-020-00282-2 source

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  • May combine two claims.

    Premisecitation

    Capnocytophaga species are saccharolytic organisms that have been shown to demonstrate increased proteolytic potential in the presence of elevated glucose levels.

    “Capnocytophaga species are saccharolytic organisms that have been shown to demonstrate increased proteolytic potential in the presence of elevated glucose levels.220”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [220] Spratt DA, Greenman J, Schaffer AG. Capnocytophaga gingivalis: effects of glucose concentration on growth and hydrolytic enzyme production. Microbiology. 1996; 142(8): 2161‐ 2164. 10.1099/13500872-142-8-2161 8760930 source

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  • May combine two claims.

    Premisecitation

    Differences in the composition of subgingival plaque have been found among patients with periodontitis, with or without type 2 diabetes; specifically, patients with diabetes harbor higher proportions of Capnocytophaga species, F nucleatum, Eikenella corrodens, and A actinomycetemcomitans than patients without diabetes.

    “Differences in the composition of subgingival plaque have been found among patients with periodontitis, with or without type 2 diabetes; specifically, patients with diabetes harbor higher proportions of Capnocytophaga species, F nucleatum, Eikenella corrodens, and A actinomycetemcomitans than patients without diabetes.219”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [219] Casarin RCV, Barbagallo A, Meulman T, et al. Subgingival biodiversity in subjects with uncontrolled type‐2 diabetes and chronic periodontitis. J Periodontal Res. 2013; 48(1): 30‐ 36. 10.1111/j.1600-0765.2012.01498.x 22762355 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    E corrodens is associated with chronic and aggressive periodontitis.

    “Moreover, E corrodens is associated with chronic and aggressive periodontitis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The oral cavity as a microbial environment is complicated by spatial gradients created by salivary flow, nutrient availability, oxygen concentration, saliva, and gingival crevicular fluids, in addition to regular environmental disturbances caused by eating and mastication, facial movement related to speaking and expression, and oral hygiene practices.

    “The oral cavity as a microbial environment is further complicated by spatial gradients created by salivary flow, nutrient availability, oxygen concentration, saliva, and gingival crevicular fluids,61, 227, 231, 232 in addition to regular environmental disturbances caused by eating and mastication, facial movement related to speaking and expression, and oral hygiene practices.227”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [61] Mark Welch JL, Rossetti BJ, Rieken CW, Dewhirst FE, Borisy GG. Biogeography of a human oral microbiome at the micron scale. Proc Natl Acad Sci USA. 2016; 113(6): E791‐ E800. 10.1073/pnas.1522149113 26811460 PMC4760785 source

      Not checked in the free run.

    • cites [227] Mark Welch JL, Dewhirst FE, Borisy GG. Biogeography of the oral microbiome: the site‐specialist hypothesis. Annu Rev Microbiol. 2019; 73(1): 335‐ 358. 10.1146/annurev-micro-090817-062503 31180804 PMC7153577 source

      Not checked in the free run.

    • cites [231] Proctor DM, Fukuyama JA, Loomer PM, et al. A spatial gradient of bacterial diversity in the human oral cavity shaped by salivary flow. Nat Commun. 2018; 9: 10.1038/s41467-018-02900-1 PMC5813034 29445174 source

      Not checked in the free run.

    • cites [232] Bowen WH, Burne RA, Wu H, Koo H. Oral biofilms: pathogens, matrix, and polymicrobial interactions in microenvironments. Trends Microbiol. 2018; 26(3): 229‐ 242. 10.1016/j.tim.2017.09.008 29097091 PMC5834367 source

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  • May combine two claims.

    Premisecitation

    Many distinct microenvironments exist in the oral cavity, and these are used as distinct niches for microbial colonization.

    “Many distinct microenvironments exist in the oral cavity, and these are used as distinct niches for microbial colonization.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Fusobacterium nucleatum and A actinomycetemcomitans are well recognized in periodontal disease, and F nucleatum is noted for its role in the development of anaerobic microenvironments that facilitate the outgrowth of anaerobic periodontal pathogens.

    “Fusobacterium nucleatum and A actinomycetemcomitans are well recognized in periodontal disease,220, 221 and F nucleatum is noted for its role in the development of anaerobic microenvironments that facilitate the outgrowth of anaerobic periodontal pathogens.222”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [220] Spratt DA, Greenman J, Schaffer AG. Capnocytophaga gingivalis: effects of glucose concentration on growth and hydrolytic enzyme production. Microbiology. 1996; 142(8): 2161‐ 2164. 10.1099/13500872-142-8-2161 8760930 source

      Not checked in the free run.

    • cites [221] Gholizadeh P, Pormohammad A, Eslami H, Shokouhi B, Fakhrzadeh V, Kafil HS. Oral pathogenesis of aggregatibacter actinomycetemcomitans. Microb Pathog. 2017; 113: 303‐ 311. 10.1016/j.micpath.2017.11.001 29117508 source

      Not checked in the free run.

    • cites [222] Diaz PI, Zilm PS, Rogers AH. Fusobacterium nucleatum supports the growth of porphyromonas gingivalis in oxygenated and carbon‐dioxide‐depleted environments. Microbiology. 2002; 148(2): 467‐ 472. 10.1099/00221287-148-2-467 11832510 source

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  • May combine two claims.

    Premisecitation

    Colonization by Corynebacterium provides long filaments on which distinct microenvironments are created, and streptococci at the periphery of oral biofilms produce lactate, which serves as a preferred substrate for catabolism by Veillonella, Corynebacterium, and Eubacterium species.

    “For example, colonization by Corynebacterium provides long filaments on which distinct microenvironments are created, and streptococci at the periphery of oral biofilms produce lactate, which serves as a preferred substrate for catabolism by Veillonella, Corynebacterium, and Eubacterium species.61, 233”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [61] Mark Welch JL, Rossetti BJ, Rieken CW, Dewhirst FE, Borisy GG. Biogeography of a human oral microbiome at the micron scale. Proc Natl Acad Sci USA. 2016; 113(6): E791‐ E800. 10.1073/pnas.1522149113 26811460 PMC4760785 source

      Not checked in the free run.

    • cites [233] Lof M, Janus MM, Krom BP. Metabolic Interactions between bacteria and fungi in commensal oral biofilms. J Fungi. 2017; 3(3): 40. 10.3390/jof3030040 PMC5715944 29371557 source

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  • May combine two claims.

    Premisecitation

    Among Streptococcus species in the oral cavity, S salivarius and Streptococcus parasanguinis are specialized for colonization on tongue dorsal surfaces, whereas S sanguinis and S gordonii instead reside in dental plaque communities.

    “For example, among Streptococcus species in the oral cavity, S salivarius and Streptococcus parasanguinis are specialized for colonization on tongue dorsal surfaces, whereas S sanguinis and S gordonii instead reside in dental plaque communities.234”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [234] Eren AM, Borisy GG, Huse SM, Welch JLM. Oligotyping Analysis of the human oral microbiome. Proc Natl Acad Sci USA 2014; 111(28): E2875‐ E2884. 10.1073/pnas.1409644111 24965363 PMC4104879 source

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  • May combine two claims.

    Premisecitation

    P gingivalis stimulates the growth of T denticola via the production of isobutyric acid, and T denticola produces succinic acid that enhances the growth of P gingivalis.

    “For example, P gingivalis stimulates the growth of T denticola via the production of isobutyric acid, and T denticola produces succinic acid that enhances the growth of P gingivalis.243”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [243] Grenier D. Nutritional interactions between two suspected periodontopathogens, treponema denticola and Porphyromonas gingivalis. Infect Immun. 1992; 60(12): 5298‐ 5301. 10.1128/IAI.60.12.5298-5301.1992 1333450 PMC258310 source

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  • May combine two claims.

    Premisecitation

    Once established, the new community of bacteria then begins the process of replication, maturation, and formation of a complex biofilm that can contain hundreds of species.

    “Once established, the new community of bacteria then begins the process of replication, maturation, and formation of a complex biofilm that can contain hundreds of species.20, 239”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] Rosan B, Lamont RJ. Dental plaque formation. Microbes Infect. 2000; 2(13): 1599‐ 1607. 11113379 source

      Not checked in the free run.

    • cites [239] Marsh PD. Dental plaque as a biofilm and a microbial community‐implications for health and disease. BioMed Central. 2006; 6: 1‐ 7. 16934115 PMC2147593

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Processing of grains further impacted several additional aspects of diet, including total nutritive content, starch bioavailability, and texture.

    “Processing of grains further impacted several additional aspects of diet, including total nutritive content, starch bioavailability, and texture.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Refined sugars constitute approximately 20% of caloric intake in the United States.

    “Moreover, refined sugars constitute approximately 20% of caloric intake.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [252] Martínez Steele E, Popkin BM, Swinburn B, Monteiro CA. The share of ultra‐processed foods and the overall nutritional quality of diets in the us: evidence from a nationally representative cross‐sectional study. Popul Health Metr. 2017; 15(1): 6. 10.1186/s12963-017-0119-3 28193285 PMC5307821 source

      Not checked in the free run.

    • cites [253] Cordain L, Eaton SB, Sebastian A, et al. Origins and evolution of the western diet: health implications for the 21st century. Am J Clin Nutr. 2005; 81(2): 341‐ 354. 10.1093/ajcn.81.2.341 15699220 source

      Not checked in the free run.

    • cites [254] Halvorsrud K, Lewney J, Craig D, Moynihan PJ. Effects of starch on oral health: systematic review to inform WHO guideline. J Dent Res. 2019; 98(1): 46‐ 53. 10.1177/0022034518788283 30074866 source

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  • May combine two claims.

    Premisecitation

    Biofilms become more pathologic as maturation progresses, with the proportion of pathogenic species increasing over time as the maturing biofilm selects for anaerobic species through metabolic and physical interactions.

    “Biofilms become more pathologic as maturation progresses, with the proportion of pathogenic species increasing over time as the maturing biofilm selects for anaerobic species through metabolic and physical interactions.232, 240”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [232] Bowen WH, Burne RA, Wu H, Koo H. Oral biofilms: pathogens, matrix, and polymicrobial interactions in microenvironments. Trends Microbiol. 2018; 26(3): 229‐ 242. 10.1016/j.tim.2017.09.008 29097091 PMC5834367 source

      Not checked in the free run.

    • cites [240] Hajishengallis G, Lamont RJ. Dancing with the stars: how choreographed bacterial interactions dictate nososymbiocity and give rise to keystone pathogens, accessory pathogens, and pathobionts. Trends Microbiol. 2016; 24(6): 477‐ 489. 10.1016/j.tim.2016.02.010 26968354 PMC4874887 source

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  • May combine two claims.

    Premisecitation

    Such changes in the pre-Neolithic oral microbiota have been further exacerbated by the evolution of food-processing techniques that emerged during the Industrial Revolution, ~200 years ago, consistent with the invention of mechanical steel roller mills in the 19th century, in which the nutritive properties of grains were significantly altered by the isolation of starch-rich components and removal

    “Such changes in the pre‐Neolithic oral microbiota have been further exacerbated by the evolution of food‐processing techniques that emerged during the Industrial Revolution, ~ 200 years ago, consistent with the invention of mechanical steel roller mills in the 19th century, in which the nutritive properties of grains were significantly altered by the isolation of starch‐rich components (flour) and”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [248] Nowakowski D, Sosulski FW, Hoover R. The effect of pin and attrition milling on starch damage in hard wheat flours. Starch ‐ Stärke. 1986; 38(8): 253‐ 258. 10.1002/star.19860380802 source

      Not checked in the free run.

    • cites [249] Stark JR, Yin XS. the effect of physical damage on large and small barley starch granules. Starch ‐ Stärke. 1986; 38(11): 369‐ 374. 10.1002/star.19860381103 source

      Not checked in the free run.

    • cites [250] Li E, Dhital S, Hasjim J. Effects of grain milling on starch structures and flour/starch properties. Starch ‐ Stärke. 2014; 66(1–2): 15‐ 27. 10.1002/star.201200224 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the United States, carbohydrates constitute more than 50% of total energy intake, with refined cereal grains representing more than 85% of total cereal grains consumed.

    “In the United States, carbohydrates constitute > 50% of total energy intake, with refined cereal grains representing > 85% of total cereal grains consumed.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [252] Martínez Steele E, Popkin BM, Swinburn B, Monteiro CA. The share of ultra‐processed foods and the overall nutritional quality of diets in the us: evidence from a nationally representative cross‐sectional study. Popul Health Metr. 2017; 15(1): 6. 10.1186/s12963-017-0119-3 28193285 PMC5307821 source

      Not checked in the free run.

    • cites [253] Cordain L, Eaton SB, Sebastian A, et al. Origins and evolution of the western diet: health implications for the 21st century. Am J Clin Nutr. 2005; 81(2): 341‐ 354. 10.1093/ajcn.81.2.341 15699220 source

      Not checked in the free run.

    • cites [254] Halvorsrud K, Lewney J, Craig D, Moynihan PJ. Effects of starch on oral health: systematic review to inform WHO guideline. J Dent Res. 2019; 98(1): 46‐ 53. 10.1177/0022034518788283 30074866 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A novel role for aerobic exopolysaccharide synthesis in subgingival biofilm formation was identified, in which treatment with dextranase reduced bacterial numbers in subgingival communities, thus highlighting the importance of supragingival biofilms in the formation of subgingival biofilm.

    “Interestingly, a novel role for aerobic exopolysaccharide synthesis in subgingival biofilm formation was identified, in which treatment with dextranase reduced bacterial numbers in subgingival communities,64 thus highlighting the importance of supragingival biofilms in the formation of subgingival biofilm.64”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] Thurnheer T, Bostanci N, Belibasakis GN. Microbial dynamics during conversion from supragingival to subgingival biofilms in an in vitro model. Mol Oral Microbiol. 2016; 31(2): 125‐ 135. 10.1111/omi.12108 26033167 source

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  • May combine two claims.

    Premisecitation

    Crosstalk between complement and pattern recognition receptors in response to dysbiosis further reinforces the immunomicrobial nature of periodontitis, in which these factors permit dysbiosis via inflammatory destruction of periodontal tissues and the provision of proteinaceous metabolic by-products that further drive dysbiosis and tissue destruction.

    “Crosstalk between complement and pattern recognition receptors in response to dysbiosis further reinforces the immunomicrobial nature of periodontitis, in which these factors permit dysbiosis via inflammatory destruction of periodontal tissues and the provision of proteinaceous metabolic by‐products that further drive dysbiosis and tissue destruction.241”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [241] Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol. 2014; 35(1): 3‐ 11. 10.1016/j.it.2013.09.001 24269668 PMC3947349 source

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    Premisecitation

    The integration of periodontal pathogens, even at low abundance, is able to alter the composition of the microbiota and results in destruction of periodontal tissues by inflammatory processes that they induce.

    “The integration of periodontal pathogens, even at low abundance, is able to alter the composition of the microbiota and results in destruction of periodontal tissues by inflammatory processes that they induce.51”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Hajishengallis G, Liang S, Payne MA, et al. Low‐abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011; 10(5): 497‐ 506. 22036469 PMC3221781 source

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  • May combine two claims.

    Premisereasoning

    Via its interactions with the commensal microbiota, P gingivalis is able to promote disease by exploiting the pro-inflammatory responses of the host, through which the dysbiotic microbiota induces the pathologic bone loss characteristic of periodontitis.

    “Via its interactions with the commensal microbiota, P gingivalis is able to promote disease by exploiting the pro‐inflammatory responses of the host, through which the dysbiotic microbiota induces the pathologic bone loss characteristic of periodontitis.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Increased consumption of cereal grains at this transition was accompanied by the emergence of dental and periodontal diseases, which is further reflected by distinct shifts in the oral microbiota.

    “Increased consumption of cereal grains at this transition was accompanied by the emergence of dental and periodontal diseases, which is further reflected by distinct shifts in the oral microbiota.245, 246, 247”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [245] Aufderheide AC, Rodríguez‐Martín C, Rodriguez‐Martin C, Langsjoen O. The Cambridge Encyclopedia of Human Paleopathology. Cambridge: Cambridge University Press; 1998.

      Not checked in the free run.

    • cites [246] Grine FE, Gwinnett AJ, Oaks JH. Early hominid dental pathology: interproximal caries in 1.5 million‐year‐old paranthropus robustus from swartkrans. Arch Oral Biol. 1990; 35(5): 381‐ 386. 10.1016/0003-9969(90)90185-d 2196866 source

      Not checked in the free run.

    • cites [247] Kerr NW. Prevalence and natural history of periodontal disease in prehistoric scots (Pre‐900 AD). J Periodontal Res. 1998; 33(3): 131‐ 137. 10.1111/j.1600-0765.1998.tb02303.x 9651874 source

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    Premisecitation

    Removal of the outer bran layer depletes fiber content and decreases dietary texture due to a loss of grain integrity.

    “Removal of this outer bran layer not only depletes fiber content but decreases dietary texture due to a loss of grain integrity.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [249] Stark JR, Yin XS. the effect of physical damage on large and small barley starch granules. Starch ‐ Stärke. 1986; 38(11): 369‐ 374. 10.1002/star.19860381103 source

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    • cites [268] Grundy MM‐L, Edwards CH, Mackie AR, Gidley MJ, Butterworth PJ, Ellis PR. Re‐evaluation of the mechanisms of dietary fibre and implications for macronutrient bioaccessibility, digestion and postprandial metabolism. Br J Nutr. 2016; 116(5): 816‐ 833. 10.1017/S0007114516002610 27385119 PMC4983777 source

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    • cites [269] Dhital S, Shrestha AK, Gidley MJ. Effect of cryo‐milling on starches: functionality and digestibility. Food Hydrocoll. 2010; 24(2/3): 152‐ 163. source

      Not checked in the free run.

    • cites [270] Tran TTB, Shelat KJ, Tang D, Li E, Gilbert RG, Hasjim J. Milling of rice grains. the degradation on three structural levels of starch in rice flour can be independently controlled during grinding. J Agric Food Chem. 2011; 59(8): 3964‐ 3973. 10.1021/jf105021r 21384921 source

      Not checked in the free run.

    • cites [271] Singh N, Katyal M, Virdi AS, et al. Effect of grain hardness, fractionation and cultivars on protein, pasting and dough rheological properties of different wheat flours. Int J Food Sci Technol. 2018; 53(9): 2077‐ 2087. 10.1111/ijfs.13794 source

      Not checked in the free run.

    • cites [272] Tamaki S, Hisamatsu M, Teranishi K, Adachi T, Yamada T. Structural change of maize starch granules by ball‐mill treatment. Starch ‐ Stärke. 1998; 50(8): 342‐ 348. 10.1002/(SICI)1521-379X(199808)50:8<342:AID-STAR342>3.0.CO;2-B

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  • Classified as probably not a substantial claim.

    Interpretationcitation

    The low rates of periodontitis among bush-dwelling women compared with village women were suggested to result from both compositional and textural differences in their diets.

    “The low rates of periodontitis among bush‐dwelling women compared with women who lived in village settings was suggested to result not only from compositional differences in their diets, but also from textural differences.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [258] Crittenden AN, Sorrentino J, Moonie SA, Peterson M, Mabulla A, Ungar PS. Oral health in transition: the hadza foragers of Tanzania. PLoS One. 2017; 12(3): e0172197. 10.1371/journal.pone.0172197 28296885 PMC5351833 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice, soft or hard diets produced differential immune responses in gingival tissues, with interleukin-17-producing T cells accumulating in periodontal tissue of mice fed a hard diet in an interleukin-6-dependent manner.

    “Mice consuming soft or hard diets demonstrated differential immune responses in gingival tissues: interleukin‐17‐producing T cells accumulated (in an interleukin‐6‐dependent manner) in periodontal tissue of mice fed a hard diet.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] Dutzan N, Abusleme L, Bridgeman H, et al. On‐going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity. 2017; 46(1): 133‐ 147. 10.1016/j.immuni.2016.12.010 28087239 PMC5263257 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Total macronutrient shifts as a result of increased grain consumption at the Paleolithic-Neolithic transition are well recognized.

    “Total macronutrient shifts as a result of increased grain consumption at the Paleolithic‐Neolithic transition are well recognized.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [253] Cordain L, Eaton SB, Sebastian A, et al. Origins and evolution of the western diet: health implications for the 21st century. Am J Clin Nutr. 2005; 81(2): 341‐ 354. 10.1093/ajcn.81.2.341 15699220 source

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  • May combine two claims.

    Premisecitation

    In an additional study, homeostatic T-helper 17 cells were induced by mechanical stimuli in a microbiome-independent manner, whereas periodontitis-associated T-helper 17 cells accumulated in a microbiome-dependent manner and required both interleukin-6 and interleukin-23.

    “homeostatic T‐helper 17 cells were found to be induced by mechanical stimuli in a microbiome‐independent manner, whereas periodontitis‐associated T‐helper 17 cells were found to accumulate in a microbiome‐dependent manner and to require both interleukin‐6 and interleukin‐23.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [52] Dutzan N, Kajikawa T, Abusleme L, et al. A dysbiotic microbiome triggers T H 17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018; 10(463): eaat0797. 10.1126/scitranslmed.aat0797 30333238 PMC6330016 source

      Not checked in the free run.

    • cites [54] Dutzan N, Konkel JE, Greenwell‐Wild T, Moutsopoulos NM. Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol. 2016; 9(5): 1163‐ 1172. 10.1038/mi.2015.136 26732676 PMC4820049 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the Hadza study, men living in the bush did not uphold the same oral health status as their female counterparts, likely because of cultural influences including high honey consumption and tobacco use.

    “However, men living in the bush did not uphold the same oral health status as their female counterparts, predictively because of cultural influences, including high consumption of honey and tobacco use.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [258] Crittenden AN, Sorrentino J, Moonie SA, Peterson M, Mabulla A, Ungar PS. Oral health in transition: the hadza foragers of Tanzania. PLoS One. 2017; 12(3): e0172197. 10.1371/journal.pone.0172197 28296885 PMC5351833 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Wild animals have superior oral health status to animals living in captivity because of the absence of masticatory challenge among foods given to domestic and captive animals.

    “Wild animals have an oral health status superior to that of animals living in captivity because of the absence of masticatory challenge among foods given to domestic and captive animals.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [23] Adler CJ, Malik R, Browne GV, Norris JM. Diet may influence the oral microbiome composition in cats. Microbiome. 2016; 4: 1‐ 9. 10.1186/s40168-016-0169-y 27277498 PMC4899902 source

      Not checked in the free run.

    • cites [261] Quest BW. Oral health benefits of a daily dental chew in dogs. J Vet Dent. 2013; 30(2): 84‐ 87. 10.1177/089875641303000203 24006717 source

      Not checked in the free run.

    • cites [263] Clarke D, Cameron A. Relationship between diet, dental calculus and periodontal disease in domestic and feral cats in Australia. Aust Vet J. 1998; 76(10): 690‐ 693. 10.1111/j.1751-0813.1998.tb12284.x 9830570 source

      Not checked in the free run.

    • cites [264] Kapoor V, Antonelli T, Parkinson JA, Hartstone‐Rose A. oral health correlates of captivity. Res Vet Sci. 2016; 107: 213‐ 219. 10.1016/j.rvsc.2016.06.009 27473998 source

      Not checked in the free run.

    • cites [265] Antonelli T, Leischner C, Ososky J, Hartstone‐Rose A. The Effect of captivity on the oral health of the critically endangered black‐footed ferret (Mustela Nigripes). Can J Zool. 2015; 94: 10.1139/cjz-2015-0135

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mechanical damage induced by consumption of foods with increased texture led to elevated expression of epithelial defensins and neutrophil chemoattractants and promoted increased neutrophil counts in gingival tissues.

    “mechanical damage induced by consumption of foods with increased texture led to elevated expression of epithelial defensins and neutrophil chemoattractants and promoted increased neutrophil counts in gingival tissues.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] Dutzan N, Abusleme L, Bridgeman H, et al. On‐going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity. 2017; 46(1): 133‐ 147. 10.1016/j.immuni.2016.12.010 28087239 PMC5263257 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The nutritional value of grains is dictated by multiple factors, including grain particle size (degree of processing) and preparation method (cooking).

    “However, the nutritional value of grains is dictated by multiple factors, including grain particle size (ie, degree of processing) and preparation method (ie, cooking).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [250] Li E, Dhital S, Hasjim J. Effects of grain milling on starch structures and flour/starch properties. Starch ‐ Stärke. 2014; 66(1–2): 15‐ 27. 10.1002/star.201200224 source

      Not checked in the free run.

    • cites [266] Romano A, Mackie A, Farina F, Aponte M, Sarghini F, Masi P. Characterisation, in vitro digestibility and expected glycemic index of commercial starches as uncooked ingredients. J Food Sci Technol. 2016; 53(12): 4126‐ 4134. 10.1007/s13197-016-2375-9 28115752 PMC5223246 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The transition from hunter-gatherer lifestyles to farming societies is associated with a decline in oral health and several additional disease states, including cardiovascular disease, inflammatory bowel diseases, rheumatic diseases, many cancers, and obesity.

    “The transition from hunter‐gatherer lifestyles to farming societies is associated with a decline in oral health as well as several additional disease states, including (but not limited to) cardiovascular disease, inflammatory bowel diseases, rheumatic diseases, many cancers, and obesity.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [24] Adler CJ, Dobney K, Weyrich LS, et al. Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the neolithic and industrial revolutions. Nat Genet. 2013; 45(4): 450‐ 455. 10.1038/ng.2536 23416520 PMC3996550 source

      Not checked in the free run.

    • cites [245] Aufderheide AC, Rodríguez‐Martín C, Rodriguez‐Martin C, Langsjoen O. The Cambridge Encyclopedia of Human Paleopathology. Cambridge: Cambridge University Press; 1998.

      Not checked in the free run.

    • cites [253] Cordain L, Eaton SB, Sebastian A, et al. Origins and evolution of the western diet: health implications for the 21st century. Am J Clin Nutr. 2005; 81(2): 341‐ 354. 10.1093/ajcn.81.2.341 15699220 source

      Not checked in the free run.

    • cites [257] Carrera‐Bastos P, Fontes‐Villalba M, O’Keefe JH, Lindeberg S, Cordain L. The western diet and lifestyle and diseases of civilization, https://www.dovepress.com/the‐western‐diet‐and‐lifestyle‐and‐diseases‐of‐civilization‐peer‐reviewed‐article‐RRCC. Accessed Jun 15, 2019. 10.2147/RRCC.S16919 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When combined with sucrose, fiber significantly increased species richness, compared with a decrease in the Firmicutes to Bacteroides ratio prompted by a sucrose-only diet.

    “When combined with sucrose, fiber significantly increased species richness, compared with a decrease in the Firmicutes to Bacteroides ratio prompted by a sucrose‐only diet.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [278] Sedghi L, Byron C, Jennings R, Chlipala GE, Green SJ, Silo‐Suh L. Effect of dietary fiber on the composition of the murine dental microbiome. Dent J. 2019; 7(2): 58. 10.3390/dj7020058 PMC6630570 31159370 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    These findings have implications for altering microbial dysbiosis elicited by modern-day diets.

    “These findings have implications for altering microbial dysbiosis elicited by modern‐day diets”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Digestion of starch is initiated in the oral cavity by salivary alpha-amylase, which catalyzes hydrolysis of starch by cleaving alpha-1,4-glycosidic linkages to yield smaller saccharide moieties such as maltose, maltotriose, and alpha-limit dextrins, which can be utilized by early biofilm colonizers and some periodontal pathogens.

    “Digestion of starch is initiated in the oral cavity through the action of salivary alpha‐amylase that catalyzes the hydrolysis of starch by cleaving α‐1,4‐glycosidic linkages to yield smaller saccharide moieties, such as maltose, maltotriose, and alpha‐limit dextrins,279, 280 which can be utilized by early biofilm colonizers as well as by some periodontal pathogens.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [279] Freitas D, Le Feunteun S. Oro‐gastro‐intestinal digestion of starch in white bread, wheat‐based and gluten‐free pasta: unveiling the contribution of human salivary α‐amylase. Food Chem. 2019; 274: 566‐ 573. 10.1016/j.foodchem.2018.09.025 30372980 source

      Not checked in the free run.

    • cites [280] Bornhorst GM, Singh RP. Bolus formation and disintegration during digestion of food carbohydrates. Compr Rev Food Sci Food Saf. 2012; 11(2): 101‐ 118. 10.1111/j.1541-4337.2011.00172.x source

      Not checked in the free run.

    • cites [8] Takahashi N. Oral Microbiome metabolism: from “who are they?” To “what are they doing?”. J Dent Res 2015; 94(12): 1628‐ 1637. 10.1177/0022034515606045 26377570 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Consumption of whole grains and fruit has been shown to reduce periodontal disease progression and improve periodontal disease status among high-risk subjects.

    “Consumption of whole grains and fruit has also been shown to reduce periodontal disease progression and improve periodontal disease status among high‐risk subjects.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [273] Schwartz N, Kaye EK, Nunn ME, Spiro A, Garcia RI. High‐fiber foods reduce periodontal disease progression in men aged 65 and older: the veterans affairs normative aging study/dental longitudinal study. J Am Geriatr Soc. 2012; 60(4): 676‐ 683. 10.1111/j.1532-5415.2011.03866.x 22316111 source

      Not checked in the free run.

    • cites [275] Kondo K, Ishikado A, Morino K, et al. A high‐fiber, low‐fat diet improves periodontal disease markers in high‐risk subjects: a pilot study. Nutr Res. 2014; 34(6): 491‐ 498. 10.1016/j.nutres.2014.06.001 25026916 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The Agricultural and Industrial Revolutions resulted in historic boosts of sugar intake, and rates of sugar intake have been rising ever since.

    “The Agricultural (~10,000 years ago) and Industrial (~200 years ago) Revolutions resulted in historic boosts of sugar intake, and the rates of sugar intake have been rising ever since.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Baker JL, Edlund A. Exploiting the oral microbiome to prevent tooth decay: has evolution already provided the best tools? Front Microbiol. 2019; 9: 3323. 30687294 PMC6338091 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A 2014 study estimated that added sugar consumption among adults in the United States has increased by more than 30% over the last 3 decades alone.

    “A 2014 study estimated that added sugar consumption among adults in the US has increased by more than 30% over the last 3 decades alone.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [283] Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2014; 384(9945): 766‐ 781. 24880830 PMC4624264 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the Baumgartner study, although plaque amount was higher at endpoint than baseline, decreased bleeding on probing and periodontal pocket depths were noted and, despite abstinence from oral hygiene, gingival inflammation did not increase.

    “Although the amount of plaque on teeth was higher at the experiment endpoint than at baseline, decreased bleeding on probing and periodontal pocket depths were noted and, despite abstinence from oral hygiene, gingival inflammation did not increase.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [251] Baumgartner S, Imfeld T, Schicht O, Rath C, Persson RE, Persson GR. The impact of the stone age diet on gingival conditions in the absence of oral hygiene. J Periodontol. 2009; 80(5): 759‐ 768. 10.1902/jop.2009.080376 19405829 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Saccharolytic bacteria, including Streptococcus, Actinomyces, and Veillonella species, degrade carbohydrates via Embden-Meyerhof-Parnas pathways to produce acidic by-products including lactate, acetate, ethanol, and formate, which cause demineralization of dental enamel and development of carious lesions.

    “Saccharolytic bacteria, including Streptococcus, Actinomyces, and Veillonella species, degrade carbohydrates via the Embden‐Meyerhof‐Parnas pathways to produce acidic by‐products, including lactate, acetate, ethanol, and formate, which cause demineralization of dental enamel and the development of carious lesions.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [22] Moye ZD, Zeng L, Burne RA. Fueling the caries process: carbohydrate metabolism and gene regulation by Streptococcus mutans. J Oral Microbiol. 2014; 6(1): 24878. PMC4157138 25317251 source

      Not checked in the free run.

    • cites [188] Koo H, Xiao J, Klein MI, Jeon JG. Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms. J Bacteriol. 2010; 192(12): 3024‐ 3032. 10.1128/JB.01649-09 20233920 PMC2901689 source

      Not checked in the free run.

    • cites [286] Klein MI, Duarte S, Xiao J, Mitra S, Foster TH, Koo H. Structural and molecular basis of the role of starch and sucrose in Streptococcus mutans biofilm development. Appl Environ Microbiol. 2009; 75(3): 837‐ 841. 10.1128/AEM.01299-08 19028906 PMC2632160 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    During normal use, toothbrushes become heavily contaminated from sources including the oral cavity, environment, hands, aerosol, and storage containers.

    “A previous review highlights that during normal use, toothbrushes become heavily contaminated from sources including the oral cavity, environment, hands, aerosol, and storage containers.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Frazelle MR, Munro CL. Toothbrush contamination: a review of the literature. Nurs Res Pract. 2012; 2012: 1‐ 6. PMC3270454 22315679 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Opportunistic oral bacteria, including Veillonella parvula, Capnocytophaga gingivalis, Leptotrichia buccalis, and Prevotella melaninogenia, were overrepresented in bronchoalveolar lavage fluid of patients with COVID-19, suggesting that the oral cavity may serve as a reservoir of bacteria implicated in coinfection with SARS-CoV-2.

    “Opportunistic oral bacteria, including Veillonella parvula, Capnocytophaga gingivalis, Leptotrichia buccalis, and Prevotella melaninogenia were overrepresented in bronchoalveolar lavage fluid of patients with COVID‐19, suggesting that the oral cavity may serve as a reservoir of bacteria implicated in coinfection with SARS‐CoV‐2 in COVID‐19.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [310] Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020; 579(7798): 265‐ 269. 10.1038/s41586-020-2008-3 32015508 PMC7094943 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Angiotensin-converting enzyme 2, the receptor that mediates entry of SARS-CoV-2 into cells, is expressed in the oral mucosa and is enriched in human tongue cells among both gustatory and nongustatory tongue epithelium.

    “Angiotensin‐converting enzyme 2, the receptor that mediates entry of SARS‐CoV‐2 into cells, is expressed in the oral mucosa and is enriched in human tongue cells among both gustatory and nongustatory tongue epithelium.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [300] Wang Z, Zhou J, Marshall B, Rekaya R, Ye K, Liu H‐X. SARS‐CoV‐2 receptor ACE2 is enriched in a subpopulation of mouse tongue epithelial cells in nongustatory papillae but not in taste buds or embryonic oral epithelium. ACS Pharmacol Transl Sci. 2020; 10: 1‐ 8. 10.1021/acsptsci.0c00062 PMC7409941 32821883

      Not checked in the free run.

    • cites [301] Shigemura N, Takai S, Hirose F, Yoshida R, Sanematsu K, Ninomiya Y. Expression of renin‐angiotensin system components in the taste organ of mice. Nutrients. 2019; 11(9): 2251. 10.3390/nu11092251 PMC6770651 31546789 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Additional associations were made between bacterial taxa on the tongue dorsum and vegetable-rich diets (such as Prevotella) or diets rich in proteins and fats (such as Clostridia).

    “Additional associations were made between the bacterial taxa on the tongue dorsum and vegetable‐rich diets (such as Prevotella) or diets rich in proteins and fats (such as Clostridia).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [295] Cattaneo C, Riso P, Laureati M, Gargari G, Pagliarini E. Exploring associations between interindividual differences in taste perception, oral microbiota composition, and reported food intake. Nutrients. 2019; 11(5): 1167. PMC6567015 31137674 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Toothbrushes have been used since the 19th century for a variety of oral health-related purposes.

    “Toothbrushes have been used since the 19th century for a variety of oral health‐related purposes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [312] Stuart LF. The history of oral hygiene products: how far have we come in 6000 Years? Periodontol 2000. 1997; 15: 7‐ 14. 9643227 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The exopolysaccharide matrix and related glucan constituents synthesized by glucosyltransferases provide binding sites for further bacterial colonization and contribute to resilience, bulk, and physical integrity of biofilm communities.

    “The exopolysaccharide matrix and related glucan constituents synthesized by glucosyltransferases provide binding sites for further bacterial colonization and contribute to the resilience, bulk, and physical integrity of biofilm communities.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [188] Koo H, Xiao J, Klein MI, Jeon JG. Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms. J Bacteriol. 2010; 192(12): 3024‐ 3032. 10.1128/JB.01649-09 20233920 PMC2901689 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The carbohydrate catabolite repression gene ccpA is located upstream of the S mutans bacteriocin production regulon and regulates its expression by controlling expression of S mutans competence stimulating peptide.

    “The carbohydrate catabolite repression gene, catabolite control protein A (ccpA), is located upstream of the S mutans bacteriocin production regulon and has been shown to regulate the expression of this by controlling the expression of S mutans competence stimulating peptide.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [292] Abranches J, Nascimento MM, Zeng L, et al. CcpA regulates central metabolism and virulence gene expression in Streptococcus mutans. J Bacteriol. 2008; 190(7): 2340‐ 2349. 18223086 PMC2293215 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    COVID-19, caused by SARS-CoV-2, is associated with many symptoms including sore throat, dry cough, muscle aches, chills, and enteric symptoms including diarrhea, nausea, and vomiting.

    “The coronavirus disease 2019 (COVID‐19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is associated with many symptoms including sore throat, dry cough, muscle aches, and chills, as well as enteric symptoms including diarrhea, nausea, and vomiting.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [296] CDC. Coronavirus Disease 2019 (COVID‐19). https://www.CDC.gov/coronavirus/2019‐ncov/daily‐life‐coping/stress‐coping/index.html. Accessed Sep 27, 2020

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The American Dental Association recommends replacing one's toothbrush every 3-4 months, or once bristles become worn out.

    “The American Dental Association recommends replacing one's toothbrush every 3‐4 months, or once bristles become worn out.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Terezhalmy GT, Bsoul SA, Bartizek RD, Biesbrock AR. Plaque removal efficacy of a prototype manual toothbrush versus an ADA reference manual toothbrush with and without dental floss. J Contemp Dent Pr. 2005; 6(3): 1‐ 13. 16127467 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent study of healthy subjects defined as nontasters or supertasters examined the potential link between taste and the tongue microbiota.

    “A recent study of healthy subjects defined as nontasters or supertasters (medium tasters were excluded) examined the potential link between taste and the tongue microbiota.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Cattaneo C, Gargari G, Koirala R, et al. New insights into the relationship between taste perception and oral microbiota composition. Sci Rep. 2019; 9(1): 1‐ 8. 30837660 PMC6401163 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Previous studies have demonstrated that toothbrushes can inoculate the oral cavity with microorganisms, but there has been little research on how microbes harbored on the toothbrush influence the oral microbiota as a whole.

    “Previous studies have demonstrated that toothbrushes can inoculate the oral cavity with microorganisms, but there has been little research on how the microbes harbored on the toothbrush influence the oral microbiota as a whole.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Bunetel L, Tricot‐Doleux S, Agnani G, Bonnaure‐Mallet M. In vitro evaluation of the retention of three species of pathogenic microorganisms by three different types of toothbrush. Oral Microbiol Immunol. 2000; 15(5): 313‐ 316. 11154423 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lower thresholds for sweet, sour, salty, and bitter tastes were observed for supertasters than for tasters, and density of fungiform papillae was higher in supertasters.

    “Lower thresholds for sweet, sour, salty, and bitter tastes were observed for supertasters than for tasters, and the density of fungiform papillae was higher in supertasters.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Cattaneo C, Gargari G, Koirala R, et al. New insights into the relationship between taste perception and oral microbiota composition. Sci Rep. 2019; 9(1): 1‐ 8. 30837660 PMC6401163 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A symptom more specific to COVID-19 infection is loss of taste and smell, in which loss of taste, or dysgeusia, occurs in approximately 88.8% of cases.

    “a symptom more specific to COVID‐19 infection is loss of taste and smell, in which loss of taste, or dysgeusia, occurs in approximately 88.8% of cases.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [297] Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and COVID‐19 in patients presenting with influenza‐like symptoms. Int Forum Allergy Rhinol. 2020; 10(7): 806‐ 813. 10.1002/alr.22579 32279441 PMC7262089 source

      Not checked in the free run.

    • cites [298] Lozada‐Nur F, Chainani‐Wu N, Fortuna G, Sroussi H. Dysgeusia in COVID‐19: possible mechanisms and implications. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020; 130(3): 344‐ 346. 10.1016/j.oooo.2020.06.016 32703719 PMC7320705 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chemosensory deficits in COVID-19 are often short-lived, with most symptoms resolving in 7-10 days, and sense of smell often returning slightly earlier than taste.

    “Such chemosensory deficits experienced in COVID‐19 are often short‐lived, with most symptoms resolving in 7‐10 days, with sense of smell often returning slightly earlier than taste.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [299] Butowt R, von Bartheld CS. Anosmia in COVID‐19: underlying mechanisms and assessment of an olfactory route to brain infection. Neuroscientist. 2020. 10.1177/1073858420956905 PMC7488171 32914699 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    Full knowledge of the role of the oral microbiome in health, and methods to modulate these ecosystems, can provide an alternative approach to disease prevention and treatment.

    “Full knowledge of the role of the oral microbiome in health, and methods to modulate these ecosystems, can provide an alternative approach to disease prevention and treatment.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Everything in the gut must pass through the oral cavity.
    • Rests on an assumption: Advancements in sequencing technologies combined with longitudinal multimodal approaches have increased understanding of the role of the oral microbiome in health and in systemic diseases.
    • Rests on an assumption: Evidence connecting dysbiosis of the oral microbiome and various systemic diseases has raised awareness of the importance of the oral microbiome in regulating health.

  • May combine two claims.

    Premisecitation

    The toothpastes reduced bacterial numbers to differing degrees: ingredients in the Chinese toothpaste, such as honeysuckle, pseudo-ginseng, and mint, which replace antibacterial ingredients like sodium fluoride, permitted growth of higher numbers of bacteria.

    “The toothpastes reduced bacterial numbers to differing degrees: ingredients in the Chinese toothpaste, such as honeysuckle, pseudo‐ginseng, and mint, which replace antibacterial ingredients like sodium fluoride, permitted growth of higher numbers of bacteria.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Shang Q, Gao Y, Qin T, Wang S, Shi Y, Chen T. Interaction of oral and toothbrush microbiota affects oral cavity health. Front Cell Infect Microbiol. 2020; 10: 17. 32117797 PMC7011102 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chlorhexidine digluconate is one of the most frequently used agents to kill bacteria, especially in dental clinics, and has potent broad-spectrum antiseptic properties against gram-positive and gram-negative bacteria.

    “Chlorhexidine digluconate is one of the most frequently used agents to kill bacteria, especially in dental clinics, and has potent broad‐spectrum antiseptic properties against gram‐positive and gram‐negative bacteria.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Jain A, Bhaskar DJ, Gupta D, et al. Comparative evaluation of honey, chlorhexidine gluconate (0.2%) and combination of xylitol and chlorhexidine mouthwash (0.2%) on the clinical level of dental plaque: a 30 days randomized control trial. Perspect Clin Res. 2015; 6(1): 53. 25657903 PMC4314848 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These microbial changes were accompanied by significant reductions in salivary pH and saliva buffering capacity and increased salivary lactate.

    “These changes were accompanied by significant reductions in salivary pH and saliva buffering capacity and increased salivary lactate.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Jain A, Bhaskar DJ, Gupta D, et al. Comparative evaluation of honey, chlorhexidine gluconate (0.2%) and combination of xylitol and chlorhexidine mouthwash (0.2%) on the clinical level of dental plaque: a 30 days randomized control trial. Perspect Clin Res. 2015; 6(1): 53. 25657903 PMC4314848 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These results demonstrate the existence of organisms with convincing anti-caries phenotypes that may be leveraged to establish healthy oral microbiomes.

    “These results thus demonstrate the existence of organisms with convincing anti‐caries phenotypes that may be leveraged to establish healthy oral microbiomes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The protease termed challisin was first discovered in a certain S gordonii strain and was thought to be specific to this organism.

    “This protease, termed challisin, was first discovered in a certain S gordonii strain and was thought to be specific to this organism.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [317] Wang B‐Y, Kuramitsu HK. Interactions between oral bacteria: inhibition of streptococcus mutans bacteriocin production by Streptococcus gordonii. Appl Environ Microbiol. 2005; 71(1): 354‐ 362. 15640209 PMC544254 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Reduced salivary pH, increased salivary lactate, and reduction in the buffering capacity of saliva are associated with tooth decay and periodontal diseases.

    “Reduced salivary pH, increased salivary lactate, and reduction in the buffering capacity of saliva are associated with tooth decay and periodontal diseases.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Jain A, Bhaskar DJ, Gupta D, et al. Comparative evaluation of honey, chlorhexidine gluconate (0.2%) and combination of xylitol and chlorhexidine mouthwash (0.2%) on the clinical level of dental plaque: a 30 days randomized control trial. Perspect Clin Res. 2015; 6(1): 53. 25657903 PMC4314848 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Organisms with convincing anti-caries phenotypes exist and may be leveraged to establish healthy oral microbiomes.

    “thus demonstrate the existence of organisms with convincing anti‐caries phenotypes that may be leveraged to establish healthy oral microbiomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The novel Streptococcus strain A12 strongly expressed the arginine deaminase pathway and produced hydrogen peroxide in large quantities along with specific virulence factors that could arrest S mutans growth and interrupt S mutans signaling pathways.

    “In addition to strongly expressing the arginine deaminase pathway, the novel strain of Streptococcus, called A12, produced hydrogen peroxide in large quantities along with specific virulence factors that could arrest S mutans growth and interrupt S mutans signaling pathways.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Huang X, Palmer SR, Ahn S‐J, et al. A Highly arginolytic streptococcus species that potently antagonizes Streptococcus mutans. Appl Environ Microbiol. 2016; 82(7): 2187‐ 2201. 26826230 PMC4807514 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The oral microbiome plays a crucial role in initiating food digestion and maintaining oral and systemic health.

    “due to improved understanding of the crucial role played by the oral microbiome in initiating food digestion and maintaining oral and systemic health.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Deo PN, Deshmukh R. Oral microbiome: unveiling the fundamentals. J Oral Maxillofac Pathol. 2019; 23(1): 122. PMC6503789 31110428 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Administration of arginine alone has been shown to be effective at inhibiting initiation of dental caries, and arginine has recently been included as a supplement in some toothpastes.

    “Administration of arginine alone has been shown to be effective at inhibiting the initiation of dental caries, and arginine has recently been included as a supplement in some toothpastes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [315] Hyde ER, Andrade F, Vaksman Z, et al. Metagenomic analysis of nitrate‐reducing bacteria in the oral cavity: implications for nitric oxide homeostasis. PLoS One. 2014; 9(3): e88645. 24670812 PMC3966736 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chlorhexidine is highly adherent to oral surfaces, making it an effective plaque-disrupting agent.

    “It is also highly adherent to oral surfaces, making it an effective plaque‐disrupting agent.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Jain A, Bhaskar DJ, Gupta D, et al. Comparative evaluation of honey, chlorhexidine gluconate (0.2%) and combination of xylitol and chlorhexidine mouthwash (0.2%) on the clinical level of dental plaque: a 30 days randomized control trial. Perspect Clin Res. 2015; 6(1): 53. 25657903 PMC4314848 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both traditional Chinese medicine and antibacterial toothpastes effectively reduced numbers of a selection of pathogenic bacteria but also suppressed oral S salivarius and L salivarius, both considered beneficial.

    “While both types of toothpaste effectively reduced the numbers of a selection of pathogenic bacteria, they also suppressed oral S salivarius and L salivarius, both of which are considered beneficial.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Shang Q, Gao Y, Qin T, Wang S, Shi Y, Chen T. Interaction of oral and toothbrush microbiota affects oral cavity health. Front Cell Infect Microbiol. 2020; 10: 17. 32117797 PMC7011102 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Streptococcus mutans is a key contributor to dental biofilms associated with formation of dental caries and plays a major role in development and establishment of extracellular polysaccharide matrices, which increase virulence of the biofilm and facilitate persistence of an acidic environment in the mouth.

    “Streptococcus mutans is a key contributor to dental biofilms associated with the formation of dental caries,44 and plays a major role in the development and establishment of extracellular polysaccharide matrices, which increase the virulence of the biofilm and facilitate persistence of an acidic environment in the mouth.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [44] Beighton D. The complex oral microflora of high‐risk individuals and groups and its role in the caries process. Community Dent Oral Epidemiol. 2005; 33(4): 248‐ 255. 16008631 source

      Not checked in the free run.

    • cites [316] Koo H, Xiao J, Klein M, Jeon J. Exopolysaccharides produced by streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms. J Bacteriol. 2010; 192(12): 3024‐ 3032. 20233920 PMC2901689 source

      Not checked in the free run.

139 of 139

  • The paper relies on this without support.

    Findings from animal models, such as germ-free mice, about oral bacteria and systemic inflammation can be extrapolated to human disease.

    “For instance, Klebsiella species isolated from the oral cavities of patients with Crohn's disease have been shown to be effective colonizers of the gut of germ‐free mice.39”
    “Studies in mice have shown that oral P gingivalis consistently invades the brain in a gingipain‐assisted manner, and that injection of gingipains into the brain increases neuronal degeneration to a level higher than that found in controls.213”

  • The paper relies on this without support.

    Findings from animal studies on dietary texture and periodontal immunity are applicable to humans.

    “The benefits of dietary texture on oral health are more commonly recognized among animal studies.”
    “Cumulatively, these findings offer a greater mechanistic understanding of how dietary nutrition and texture alike alter the oral microbiota and immune response at the gingiva.”

  • The paper relies on this without support.

    The Hadza villagers consuming an agricultural diet represent a Westernized dietary influence, and bush dwellers represent ancestral diets.

    “An oral health study among the Hadza hunter‐gatherers of Tanzania offered a rare opportunity to study the impact of ancestral diets among “bush dwellers” and increasingly Westernized diets on the oral health status among “villagers.””

  • The paper relies on this without support.

    Everything in the gut must pass through the oral cavity.

    “but we must remember that everything in the gut must pass through the oral cavity.”

  • The paper relies on this without support.

    Anti-caries qualities are very specific at the species and strain levels.

    “However, these qualities are very specific at the species and strain levels, and tight quality assurance will be needed for incorporation into probiotic formulations.”

  • The paper relies on this without support.

    Advancements in sequencing technologies combined with longitudinal multimodal approaches have increased understanding of the role of the oral microbiome in health and in systemic diseases.

    “Advancements in sequencing technologies combined with longitudinal multimodal approaches have increased our understanding of the role of the oral microbiome in health and in systemic diseases.”

  • The paper relies on this without support.

    Evidence connecting dysbiosis of the oral microbiome and various systemic diseases has raised awareness of the importance of the oral microbiome in regulating health.

    “Evidence connecting the relationship between dysbiosis of the oral microbiome and various systemic diseases has raised awareness of the importance of the oral microbiome in regulating health.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Research works printed but not linked: 11

  1. d’Ettorre G, 2019, Ectopic colonization of oral bacteria in the intestine drives Th1 cell induction and. Inflammation, Science, 358, 359
  2. 10.1038/sj.bdj.2016.865 · DOI · Paper page
  3. Proteomics ‐ an overview | ScienceDirect Topic
  4. 10.1093/ajh/hpu192 · DOI · Paper page
  5. 10.1038/ijos.2014.48 · DOI · Paper page
  6. De Pablo P, 2008, Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population, J Rheumatol, 35, 70
  7. Gerrior S, 2002, Nutrient Content of the U.S. Food Supply, 1909–99: A Summary Report; Center for Nutrition Policy and Promotion
  8. Natella S, Sugar Consumption at a Crossroads
  9. Obiefuna S, 2020, StatPearls
  10. 10.3389/fphys.2019.01029 · DOI · Paper page
  11. 10.1128/JB.01649-09 · DOI · Paper page

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Related

Authors
Sedghi, L., DiMassa, V., Harrington, A., Lynch, S. V., & Kapila, Y. L.
Affiliations
University of California, San Francisco (US)
Corresponding author
Sedghi, Lea
ORCID
Venue
Periodontology 2000
Publisher
Wiley
Published
2021-08-31
Volume
87
Issue
1
Pages
107-131
ISSN
  • 0906-6713 (ISSN-L)
  • 1600-0757
DOI
10.1111/prd.12393
PMC
PMC8457218
OpenAlex
W3197883362
Semantic Scholar
ebee47d552c181ccd8c9835b95faa96ac5249d59
Cited by
755
References
315
Citations by year
2026: 160 · 2025: 207 · 2024: 194 · 2023: 113 · 2022: 76 · 2021: 5
FWCI
16.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Periodontology 2000 (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Dental and Craniofacial Research (R01DE025225, T32DE007306)
Topics
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords
oral microbiota, polymicrobial biofilms, microbial interactions, oral health, oral diseases, periodontal disease, dental diseases, dysbiosis, host-microbe interactions, salivary flow, diet, oral hygiene, mother-to-child transmission, host genetics, microbial community composition
MeSH terms
Humans, Mouth, Oral Health, Periodontal Diseases, Microbiota, Dysbiosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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