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Cited by 423Oral microbiology and periodontitis researchGut microbiota and healthDental Research and COVID-19

The oral microbiota is modified by systemic diseases.

Open access
Graves, D.T., Corrêa, J.D., Silva, T.A.·2019·Journal of Dental Research
DOI 10.1177/0022034518805739PMC PMC6761737
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Abstract

Periodontal diseases are initiated by bacteria that accumulate in a biofilm on the tooth surface and affect the adjacent periodontal tissue. Systemic diseases such as diabetes, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) increase susceptibility to destructive periodontal diseases. In human studies and in animal models, these diseases have been shown to enhance inflammation in the periodontium and increase the risk or severity of periodontitis. All 3 systemic diseases are linked to a decrease in bacterial taxa associated with health and an increase in taxa associated with disease. Although there is controversy regarding the specific oral bacterial changes associated with each disease, it has been reported that diabetes increases the levels of Capnocytophaga, Porphyromonas, and Pseudomonas, while Prevotella and Selenomonas are increased in RA and Selenomonas, Leptotrichia, and Prevotella in SLE. In an animal model, diabetes increased the pathogenicity of the oral microbiome, as shown by increased inflammation, osteoclastogenesis, and periodontal bone loss when transferred to normal germ-free hosts. Moreover, in diabetic animals, the increased pathogenicity could be substantially reversed by inhibition of IL-17, indicating that host inflammation altered the microbial pathogenicity. Increased IL-17 has also been shown in SLE, RA, and leukocyte adhesion deficiency and may contribute to oral microbial changes in these diseases. Successful RA treatment with anti-inflammatory drugs partially reverses the oral microbial dysbiosis. Together, these data demonstrate that systemic diseases characterized by enhanced inflammation disturb the oral microbiota and point to IL-17 as key mediator in this process.

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Written from the paper’s full text.

TL;DR

This review argues that systemic inflammatory diseases—diabetes, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE)—modify the oral microbiota by reducing health-associated taxa and increasing disease-associated taxa, with IL-17 proposed as a key mediator. In animal models, diabetic oral microbiota transfer increased inflammation and periodontal bone loss, and IL-17 inhibition substantially reversed this increased pathogenicity.

Key findings

  • Diabetes, RA, and SLE are linked to decreased bacterial taxa associated with health and increased taxa associated with disease; reported increases include *Capnocytophaga*, *Porphyromonas*, and *Pseudomonas* in diabetes, *Prevotella* and *Selenomonas* in RA, and *Selenomonas*, *Leptotrichia*, and *Prevotella* in SLE.
  • In diabetic mice, transfer of oral microbiota to normal germ-free hosts increased neutrophil infiltration, IL-6 and RANKL expression, osteoclast numbers, and periodontal bone loss compared with transfer from normoglycemic donors; inhibition of IL-17 shifted the microbiota toward a normoglycemic profile and reduced its capacity to stimulate inflammation and alveolar bone loss.
  • Human periodontitis data cited include 47% of US adults with evidence of periodontitis and 10% to 15% with advanced periodontitis; periodontitis subjects can show up to a 3-log increase in subgingival bacterial load. RA increased microbial biomass approximately 1-log, and a meta-analysis reported a 1.76-fold increased risk of periodontal disease in SLE subjects.
  • Successful RA treatment with anti-inflammatory drugs partially reverses oral microbial dysbiosis, and periodontal treatment improves response to conventional therapy in SLE patients with reduced disease activity.

Methods

  • Narrative review synthesizing human studies and animal models on oral microbiota changes associated with diabetes, RA, and SLE.
  • Includes discussion of a longitudinal mouse model of spontaneous diabetes and germ-free transfer experiments, plus tables summarizing bacterial community changes.
  • No new primary data are presented; the paper cites published literature and refers to some unpublished results from the authors.

Limitations

  • The paper states that human studies have not revealed consistent diabetes-induced microbial changes, citing potential false positives from large numbers of oral microorganisms, insufficient subject numbers, confounding factors such as degree of hyperglycemia, disease duration and medications, technical limitations, and limited longitudinal studies.
  • The paper states that functional studies linking specific microbiota disturbances and inflammatory pathways with periodontal damage in SLE have not been reported as they have for diabetes, and that the IL-17 hypothesis and downstream events need further investigation.
  • Evident from the text: as a narrative review, it relies on heterogeneous studies and includes unpublished results, without a described systematic search or quantitative synthesis; the paper also notes that assigning taxa as “good” and “bad” is an oversimplification.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1177/0022034518805739

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 125 cited sources checked · 0 supported · 0 flagged

  • Findingcitation
    § Abstract

    In diabetic animals, the increased pathogenicity of the oral microbiome could be substantially reversed by inhibition of IL-17.

    “Moreover, in diabetic animals, the increased pathogenicity could be substantially reversed by inhibition of IL-17, indicating that host inflammation altered the microbial pathogenicity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xiao et al. 2017

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.
  • Findingcitation
    § Abstract

    In an animal model, diabetes increased the pathogenicity of the oral microbiome, as shown by increased inflammation, osteoclastogenesis, and periodontal bone loss when transferred to normal germ-free hosts.

    “In an animal model, diabetes increased the pathogenicity of the oral microbiome, as shown by increased inflammation, osteoclastogenesis, and periodontal bone loss when transferred to normal germ-free hosts.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xiao et al. 2017

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.
  • Findingown data
    § Abstract

    Diabetes-prone and normoglycemic littermates initially had similar oral microbiomes.

    “The diabetes-prone and normoglycemic littermates initially had similar oral microbiomes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xiao et al. 2017

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    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.
  • Findingcitation
    § Abstract

    Diabetes reduced the diversity of oral microbiota.

    “Diabetes also reduced the diversity of oral microbiota as reported in other tissues where diabetes reduces bacterial diversity (Ussar et al. 2016).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Xiao et al. 2017

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    • cites Ussar et al. 2016

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    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.
  • Findingown data
    § Abstract

    IL-17 inhibition decreased the capacity of bacteria from diabetic animals to stimulate inflammation and alveolar bone loss in normal germ-free recipients.

    “IL-17 inhibition decreased the capacity of bacteria from diabetic animals to stimulate inflammation and alveolar bone loss in normal germ-free recipients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xiao et al. 2017

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    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.
  • May combine two claims. 49
  • Classified as probably not a substantial claim. 9

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    Findingcitation
    § Abstract

    Development of hyperglycemia induced a shift in the bacterial composition, increasing the levels of Proteobacteria (Enterobacteriaceae) and Firmicutes (Enterococcus, Staphylococcus, and Aerococcus) associated with pathologic changes.

    “Development of hyperglycemia induced a shift in the bacterial composition (Xiao et al. 2017), increasing the levels of Proteobacteria (Enterobacteriaceae) and Firmicutes (Enterococcus, Staphylo-coccus, and Aerococcus) associated with pathologic changes (Demmer et al. 2016; Grice et al. 2010).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Xiao et al. 2017

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    • cites Demmer et al. 2016

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    • cites Grice et al. 2010

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    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.

  • May combine two claims.

    Findingcitation
    § Abstract

    Transfer from hyperglycemic mice stimulated greater neutrophil infiltration and increased expression of bone-resorbing cytokines (IL-6 and RANKL), enhanced osteoclast numbers, and stimulated more periodontal bone loss than bacteria from normoglycemic controls.

    “Transfer from hyperglycemic mice stimulated greater neutrophil infiltration and increased expression of bone-resorbing cytokines (IL-6 and RANKL), enhanced osteoclast numbers, and stimulated more periodontal bone loss than bacteria from normoglycemic controls.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xiao et al. 2017

      Not checked in the free run.

    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.

  • May combine two claims.

    Findingcitation
    § Abstract

    When IL-17 was inhibited, the oral microbiota shifted in a direction of reduced pathogenicity and to a composition that was more similar to that of normoglycemic control animals.

    “Moreover, when IL-17 was inhibited, the oral microbiota shifted in a direction of reduced pathogenicity and to a composition that was more similar to that of normoglycemic control animals (Xiao et al. 2017), suggesting that controlling inflammation increases the likelihood of having a “nonpathogenic” oral bacterial profile.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xiao et al. 2017

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    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.

  • May combine two claims.

    Findingown data
    § Abstract

    Inhibition of IL-17 altered the microbial composition in diabetic mice so that it was more similar to the normoglycemic oral microbiota and reduced the abundance of Enterococcus in particular.

    “Inhibition of IL-17 altered the microbial composition in diabetic mice so that it was more similar to the normoglycemic oral microbiota and reduced the abundance of Enterococcus in particular.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xiao et al. 2017

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    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.

  • May combine two claims.

    Findingcitation
    § Abstract

    Aging in mice reduces oral bacterial diversity, accompanied by greater colonization of P. gingivalis when exposed to this human pathogen.

    “Interestingly, we have found that aging in mice also reduces oral bacterial diversity, which is accompanied by greater colonization of P. gingivalis when exposed to this human pathogen (Xiao et al. 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Xiao et al. 2016

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    • Rests on an assumption: Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.

  • May combine two claims.

    Findingcitation
    § Abstract

    Rheumatoid arthritis subjects show increased salivary concentration of IL-17, tumor necrosis factor-alpha, and IL-33, similar to observations in systemic lupus erythematosus.

    “RA subjects also show increased salivary concentration of IL-17, TNF-α, and IL-33 (Corrêa et al. 2018, unpublished results) similar to observations in SLE (Corrêa et al. 2017).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Corrêa et al. 2018, unpublished results

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    • cites Corrêa et al. 2017

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    Findingcitation
    § Abstract

    Rheumatoid arthritis increases the microbial biomass approximately 1-log and alters the composition with increased numbers of pathogenic bacteria.

    “We also found that RA increases the microbial biomass approximately 1-log and alters the composition with increased numbers of pathogenic bacteria (Corrêa et al. 2018, unpublished results).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Corrêa et al. 2018, unpublished results

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    Interpretationnone given
    § Abstract

    All three systemic diseases (diabetes, rheumatoid arthritis, and systemic lupus erythematosus) are linked to a decrease in bacterial taxa associated with health and an increase in taxa associated with disease.

    “All 3 systemic diseases are linked to a decrease in bacterial taxa associated with health and an increase in taxa associated with disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation
    § Abstract

    Increased IL-17 has been shown in systemic lupus erythematosus, rheumatoid arthritis, and leukocyte adhesion deficiency and may contribute to oral microbial changes in these diseases.

    “Increased IL-17 has also been shown in SLE, RA, and leukocyte adhesion deficiency and may contribute to oral microbial changes in these diseases.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Abusleme and Moutsopoulos 2017

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    Interpretationreasoning
    § Abstract

    Increased levels of periodontal disease, diabetes, systemic lupus erythematosus, and rheumatoid arthritis may reflect a common susceptibility, since each has inflammation as a common risk factor.

    “Increased levels of periodontal disease, diabetes, systemic lupus erythematosus (SLE), and RA may reflect a common susceptibility, since each has inflammation as a common risk factor.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning
    § Abstract

    The composition of the microbiota is governed by local factors, but systemic factors can also have a significant effect.

    “The composition of the microbiota is governed by local factors, but systemic factors can also have a significant effect.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Abstract

    Increased bacterial loads occur in humans with periodontitis and in mice as they age and develop periodontitis, with increased susceptibility to colonization by periodontal pathogens such as P. gingivalis.

    “This is supported by increased bacterial loads in humans with periodontitis and in mice as they age and develop periodontitis, with increased susceptibility to colonization by periodontal pathogens such as P. gingivalis (Wu et al. 2016).”
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    • cites Wu et al. 2016

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  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Interpretationcitation
    § Abstract

    An overall increase in microbial biomass, rather than a specific change in composition, may promote periodontitis.

    “An alternative hypothesis that was popular in the mid-1900s and has some recent support postulates that an overall increase in microbial biomass, rather than a specific change in composition, may promote periodontitis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wu et al. 2016

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    Interpretationreasoning
    § Abstract

    Individuals with a greater tendency toward inflammation have enhanced susceptibility and risk of periodontitis as well as increased levels of diabetes, systemic lupus erythematosus, and rheumatoid arthritis.

    “Those individuals with a greater tendency toward inflammation have enhanced susceptibility and risk of periodontitis as well as increased levels of diabetes, SLE, and RA.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § Abstract

    Systemic inflammatory diseases may increase local inflammation, which alters the expression of inflammatory mediators locally and increases recruitment of leukocytes to the periodontium.

    “One mechanism is that systemic inflammatory diseases may increase local inflammation, which alters the expression of inflammatory mediators locally and increases recruitment of leukocytes to the periodontium (see Fig. 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Abstract

    Qualitative changes occur as a result of competitiveness among species, leading to an increase in bacterial taxa that are pathogenic.

    “Qualitative changes also occur as a result of competitiveness among species (Diaz 2012; Griffen et al. 2012), leading to an increase in bacterial taxa that are pathogenic.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Diaz 2012

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    • cites Griffen et al. 2012

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    Premisecitation
    § Abstract

    Diabetes potentially affects factors that can enhance inflammation in periodontal tissues, including high glucose levels, increased formation of advanced glycation end products, and enhanced cytokine expression (e.g., tumor necrosis factor).

    “Diabetes potentially affects a number of factors that can enhance inflammation in periodontal tissues, including high glucose levels, increased formation of advanced glycation end products, and enhanced cytokine expression (e.g., tumor necrosis factor [TNF]; Wu et al. 2015).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wu et al. 2015

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    Premisecitation
    § Abstract

    Neutrophils and monocytes/macrophages from diabetic patients express higher levels of cytokines in response to stimulation and are less effective in bacterial killing.

    “Neutrophils and monocytes/macrophages from diabetic patients express higher levels of cytokines in response to stimulation and are less effective in bacterial killing (Omori et al. 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Omori et al. 2008

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  • Classified as probably not a substantial claim.

    Premisecitation
    § Abstract

    A consensus report from the European Federation of Periodontology and the American Academy of Periodontology found no compelling evidence that diabetes has a significant impact on the oral microbiota.

    “A consensus report from the European Federation of Periodontology and the American Academy of Periodontology found no compelling evidence that diabetes has a significant impact on the oral microbiota (Chapple et al. 2013).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Chapple et al. 2013

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    Interpretationcitation
    § Abstract

    Recent high-throughput analysis suggests that there may be differences between diabetic and normal cohorts, but there is yet no consensus on the changes induced.

    “Recent high-throughput analysis suggests that there may be differences between diabetic and normal cohorts, but there is yet no consensus on the changes induced, as shown in Table 1 (Casarin et al. 2012; Aemaimanan et al. 2013; Zhou et al. 2013; Merchant et al. 2014; Sakalauskiene et al. 2014; Castrillon et al. 2015; Demmer et al. 2016).”
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    • cites Aemaimanan et al. 2013

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    • cites Zhou et al. 2013

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    Interpretationreasoning
    § Abstract

    Previous human studies have not revealed consistent changes in microbial composition, in part because of the limited numbers of bacteria surveyed.

    “Thus, previous human studies have not revealed consistent changes in microbial composition, in part because of the limited numbers of bacteria surveyed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Abstract

    Type 1 and type 2 diabetes mellitus affect the periodontium in children and adults, with an increase in periodontal inflammation similar to the increased inflammation in other tissues affected by diabetes.

    “Type 1 and type 2 diabetes mellitus (T1DM and T2DM) affect the periodontium in children and adults, with an increase in periodontal inflammation similar to the increased inflammation in other tissues affected by diabetes (Wu et al. 2015).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wu et al. 2015

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    Premisecitation
    § Abstract

    In skin wounds, diabetes alters the wound microbiota, which is linked to increased inflammation.

    “In skin wounds, diabetes alters the wound microbiota, which is linked to increased inflammation (Grice et al. 2010).”
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    • cites Grice et al. 2010

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    Premisecitation
    § Abstract

    High IL-17 levels are found in humans with periodontitis, and IL-17 induces RANKL.

    “Interestingly, high IL-17 levels are found in humans with periodontitis, and IL-17 induces RANKL (Abusleme and Moutsopoulos 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Abusleme and Moutsopoulos 2017

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    Premisecitation
    § Abstract

    Butyrate-producing bacteria are reduced in individuals with type 2 diabetes mellitus, and butyrate protects against the development of diabetes; thus, reduced production of butyrate may increase risk of diabetes.

    “Butyrate-producing bacteria are reduced in individuals with T2DM, and butyrate protects against the development of diabetes (Arora and Bäckhed 2016); thus, reduced production of butyrate may increase risk of diabetes.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Abstract

    Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation.

    “RA is a systemic autoimmune disease characterized by chronic inflammation (de Smit et al. 2015).”
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    • cites de Smit et al. 2015

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    Interpretationown data
    § Abstract

    Chronic inflammation enhanced by diabetes causes microbial dysbiosis that increases bacterial pathogenicity.

    “We propose that chronic inflammation enhanced by diabetes causes microbial dysbiosis that increases bacterial pathogenicity (see Fig. 2).”
    Quote in the paperSubstantial claim

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    Premisecitation
    § Abstract

    Leukocyte adhesion deficiency in humans results in greater IL-17 production and formation of dysbiotic bacterial communities, thereby identifying IL-17 as a cause of microbial dysbiosis.

    “Leukocyte adhesion deficiency in humans results in greater IL-17 production and formation of dysbiotic bacterial communities, thereby identifying IL-17 as a cause of microbial dysbiosis (Abusleme and Moutsopoulos 2017).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation
    § Abstract

    Patients with oral lichen planus have increased disease-associated bacterial species and increased IL-17 in saliva.

    “Similarly, patients with oral lichen planus have increased disease-associated bacterial species and increased IL-17 in saliva (Wang et al. 2014).”
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    • cites Wang et al. 2014

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    Premisecitation
    § Abstract

    The gut microbiota changes with diabetes, which is subsequently altered when diabetes is reversed by bariatric surgery.

    “Similarly, the gut microbiota changes with diabetes, which is subsequently altered when diabetes is reversed by bariatric surgery (Sweeney and Morton 2013).”
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    Interpretationcitation
    § Abstract

    Oral bacteria may contribute to a bidirectional relationship between periodontal disease and diabetes, whereby changes in the oral microbiota through increased systemic inflammation enhance insulin resistance to promote hyperglycemia.

    “Oral bacteria may contribute to a bidirectional relationship between periodontal disease and diabetes, whereby changes in the oral microbiota through increased systemic inflammation enhance insulin resistance to promote hyperglycemia (as discussed by Borgnakke et al. 2013).”
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    Interpretationnone given
    § Abstract

    Oral bacteria may also have an impact on diabetes, although the evidence to support this link is limited.

    “Oral bacteria may also have an impact on diabetes, although the evidence to support this link is limited.”
    Quote in the paperNot a substantial claim

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    Interpretationcitation
    § Abstract

    There may be a bidirectional relationship between the gut microbiota and diabetes whereby diabetes alters bacterial composition and changes in bacterial profile enhance susceptibility to diabetes through a butyrate-mediated mechanism.

    “Furthermore, there may be a bidirectional relationship between the gut microbiota and diabetes whereby 1) diabetes alters bacterial composition and 2) changes in bacterial profile enhance susceptibility to diabetes through a butyrate-mediated mechanism.”
    Quote in the paperNot a substantial claim

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    Premisecitation
    § Abstract

    Treatment with oral antiseptics that reduce the total oral bacterial load protects against rheumatoid arthritis-induced periodontal bone loss, indicating a role for oral microbiota.

    “Treatment with oral antiseptics that reduce the total oral bacterial load protects against RA-induced periodontal bone loss, indicating a role for oral microbiota (Queiroz-Junior et al. 2011).”
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    • cites Queiroz-Junior et al. 2011

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    Interpretationcitation
    § Abstract

    Rheumatoid arthritis may amplify the inflammatory response in the periodontium, which in turn modifies the microbiota.

    “RA may amplify the inflammatory response in the periodontium, which in turn modifies the microbiota (Golub et al. 2006).”
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    • cites Golub et al. 2006

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    Premisecitation
    § Abstract

    Anaerobic species such as Lactobacillus salivarius, Atopobium, Leptotrichia, Prevotella, and Cryptobacterium curtum are enriched in the oral microbiota of rheumatoid arthritis patients, and health-associated Corynebacterium and Streptococcus genera are reduced.

    “Anaerobic species such as Lactobacillus salivarius, Atopobium, Leptotrichia, Prevotella, and Cryptobacterium curtum are enriched in the oral microbiota of RA patients, and health-associated Corynebacterium and Streptococcus genera are reduced (Scher et al. 2012; Zhang et al. 2015).”
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    • cites Scher et al. 2012

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    • cites Zhang et al. 2015

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    Premisecitation
    § Abstract

    Disease-modifying antirheumatic drugs reduce inflammation and severity of RA, and alter gut and oral microbiota.

    “Disease-modifying antirheumatic drugs reduce inflammation and the severity of RA, and alter the gut and oral microbiota (Zhang et al. 2015).”
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    • cites Zhang et al. 2015

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    Interpretationreasoning
    § Abstract

    In RA, increased inflammation coupled with microbial changes may amplify periodontal inflammation and explain greater susceptibility to periodontitis.

    “The increased inflammation caused by RA coupled with microbial changes may amplify periodontal inflammation and explain the greater susceptibility to periodontitis that we and others have observed in these patients (de Smit et al. 2015).”
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    • cites de Smit et al. 2015

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    Premisecitation
    § Abstract

    Prevotella copri has a high capacity to induce Th17-related cytokines, and Prevotella sp. is associated with Th17-mediated mucosal inflammation.

    “Interestingly, Prevotella copri has a high capacity to induce Th17-related cytokines, and Prevotella sp. is associated with Th17-mediated mucosal inflammation (Larsen 2017).”
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    • cites Larsen 2017

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    Interpretationreasoning
    § Abstract

    Changes in systemic and local inflammation may disrupt microbial homeostasis and consequently increase bacterial pathogenicity and periodontal disease susceptibility.

    “Therefore, changes in systemic and local inflammation may disrupt microbial homeostasis and consequently increase bacterial pathogenicity and periodontal disease susceptibility (see Table 1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Table 1

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    Premisecitation
    § Abstract

    The microbial composition of the gut in early rheumatoid arthritis differs from controls, with a reduction of Bifidobacterium and Bacteroides and an increase in Prevotella.

    “The microbial composition of the gut in early RA differs from controls, with a reduction of Bifidobacterium and Bacteroides and an increase in Prevotella (Horta-Baas et al. 2017).”
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    Interpretationreasoning
    § Abstract

    Controlling inflammation can shift the microbiota to a healthy status, restoring systemic and oral/periodontal homeostasis.

    “These results suggest that controlling inflammation can shift the microbiota to a “healthy status,” restoring systemic and oral/periodontal homeostasis.”
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    • cites Zhang et al. 2015

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    Premisecitation
    § Abstract

    RA treatment improves periodontal status and affects the oral microbiome.

    “Conversely, RA treatment improves periodontal status and affects the oral microbiome (Zhang et al. 2015).”
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    • cites Zhang et al. 2015

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    Premisecitation
    § Abstract

    Increased periodontal disease risk in SLE is associated with changes in local and systemic inflammatory pathways, demonstrated by elevated salivary cytokines (IL-6, IL-17, IL-33).

    “The increased risk is associated with changes in local and systemic inflammatory pathways, as demonstrated by elevated levels of cytokines (e.g., IL-6, IL-17, and IL-33) in the saliva of SLE patients (Marques et al. 2016; Corrêa et al. 2017; Mendonça et al. 2018).”
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    Premisecitation
    § Abstract

    Oral manifestations of SLE include unspecified oral ulcers, xerostomia, and hyposalivation.

    “In the oral cavity, the manifestations of SLE include unspecified oral ulcers (Jensen et al. 1999), xerostomia, hyposalivation (Jensen et al. 1999), and increased periodontal disease (Mutlu et al. 1993; Kobayashi et al. 2003; Corrêa et al. 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jensen et al. 1999

      Not checked in the free run.

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

    Premisecitation
    § Abstract

    SLE etiology includes genetic and environmental factors.

    “The etiology of SLE includes genetic and environmental factors (López et al. 2016) and is linked to microbial dysbiosis (Hevia et al. 2014; López et al. 2016; Corrêa et al. 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites López et al. 2016

      Not checked in the free run.

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

    Premisecitation
    § Concluding Remarks

    Several systemic diseases cause increased periodontal inflammation with the assumption that primary component was straightforward upregulation of pro-osteoclastogenic factors.

    “Furthermore, it is widely recognized that several systemic diseases cause increased periodontal inflammation with the assumption that the primary component was a straightforward upregulation of pro-osteoclastogenic factors (Xiao et al. 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Xiao et al. 2016

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationcitation
    § Concluding Remarks

    Assignment to good and bad categories is an oversimplification and needs experimental justification.

    “However, the assignment to “good” and “bad” categories is an oversimplification and needs to be experimentally justified, as recently reported for murine diabetic studies (Xiao et al. 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Xiao et al. 2017

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Abstract

    SLE subjects have reduced microbial diversity with greater proportions of pathogenic bacteria.

    “SLE subjects have reduced microbial diversity with greater proportions of pathogenic bacteria (Corrêa et al. 2017).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Corrêa et al. 2017

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Abstract

    Lupus-prone mice have depleted lactobacilli and increased Clostridial species (Lachnospiraceae) associated with overall increased bacterial diversity.

    “Lupus-prone mice have depleted lactobacilli and an increase in Clostridial species (Lachnospiraceae) associated with an overall increase in bacterial diversity (Zhang et al. 2014; Mu et al. 2017).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Zhang et al. 2014

      Not checked in the free run.

    • cites Mu et al. 2017

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning
    § Concluding Remarks

    IL-17 and other cytokines may play a pivotal role in this process.

    “IL-17 and other cytokines may play a pivotal role in this process.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Abstract

    Increasing Lactobacillales in the gut of mice by adding a mixture of 5 Lactobacillus strains improved SLE severity and prolonged survival.

    “As a proof of concept, increasing Lactobacillales in the gut of mice by adding a mixture of 5 Lactobacillus strains led to an improvement of SLE severity and prolonged survival (Mu et al. 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mu et al. 2017

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation
    § Abstract

    Increased inflammation may provide nutrients in the form of tissue breakdown products and alter the environment, favoring growth of anaerobic bacteria.

    “Increased inflammation may provide a source of nutrients in the form of tissue breakdown products and may alter the environment, favoring the growth of anaerobic bacteria (Hajishengallis 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hajishengallis 2014

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Concluding Remarks

    Microbial changes observed in systemic diseases generally reduce microbial diversity and shift bacterial composition by increasing taxa considered bad and reducing those considered good.

    “Microbial changes observed in systemic diseases generally reduce microbial diversity and shift bacterial composition by increasing taxa that are generally considered to be “bad” and reducing those that are “good” (see Table 1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Table 1

      Not checked in the free run.

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

    Interpretationnone given
    § Concluding Remarks

    Inflammatory changes may induce an amplification loop in which the bacterial component becomes more pathogenic.

    “However, this may be an oversimplification, as the inflammatory changes may induce an amplification loop in which the bacterial component becomes more pathogenic.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given
    § Concluding Remarks

    IL-17 operates in concert with other inflammatory cytokines.

    “We also recognize that IL-17 operates in concert with other inflammatory cytokines and that an overall dysregulation of these mediators may contribute to host alterations that lead to microbial dysbiosis.”
    Quote in the paperNot a substantial claim
56 of 56

  • The paper relies on this without support.

    Findings from animal models of diabetes, rheumatoid arthritis, and systemic lupus erythematosus are representative of the corresponding human systemic diseases for the purpose of inferring effects on the human oral microbiota.

    “In an animal model, diabetes increased the pathogenicity of the oral microbiome, as shown by increased inflammation, osteoclastogenesis, and periodontal bone loss when transferred to normal germ-free hosts.”
    “Together, these data demonstrate that systemic diseases characterized by enhanced inflammation disturb the oral microbiota and point to IL-17 as key mediator in this process.”
1 of 1

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?

  • The decrease in oral microbiota diversity in diabetes is associated with an increase in the pathogenic content of the hyperglycemic microbiota, such as Capnocytophaga, Porphyromonas, and Pseudomonas.

    “Moreover, it has been reported that the diversity of oral microbiota in patients with diabetes decreases significantly, and is associated with an increase in the pathogenic content of the hyperglycemic microbiota (Saeb et al., 2019), such as Capnocytophaga, Porphyromonas, and Pseudomonas (Graves et al., 2019).”

    From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Graves et al., 2019

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Prevotella maculosa is classified as both health- and periodontitis-associated

    Minor

    The paper calls P. maculosa associated with oral health when describing its increase after RA treatment, but earlier lists it among periodontitis-associated bacteria enriched in RA patients.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Borgnakke WS, 2013, J Periodontol, 84
  2. Chapple ILC, 2013, J Periodontol, 40
  3. Kinane DF, 2017, Nat Rev Dis Prim, 3
  4. Mendonça SMS, 2018, Clin Exp Rheumatol [epub ahead of print 19 Jul 2018] in press

Cited by

Sorted by citations

Related

Authors
Graves, D. T., Corrêa, J. D., & Silva, T. A.
Affiliations
  • University of Pennsylvania (US)
  • Universidade Federal de Minas Gerais (BR)
  • Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Brazil
Corresponding author
Graves, D.T.
ORCID
Venue
Journal of Dental Research
Publisher
SAGE Publications
Published
2018-10-25
Volume
98
Issue
2
Pages
148-156
ISSN
  • 0022-0345 (ISSN-L)
  • 1544-0591
DOI
10.1177/0022034518805739
PMC
PMC6761737
OpenAlex
W2898140240
Semantic Scholar
58c4ce0841a04faa6c0870ccf298d83a37a7ccd3
Cited by
423
References
72
Citations by year
2026: 56 · 2025: 71 · 2024: 59 · 2023: 61 · 2022: 56 · 2021: 68 · 2020: 36 · 2019: 14
FWCI
33.53
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Dental Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
NIH (R01 DE017732)
Topics
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Dentistry › General Dentistry › Dental Research and COVID-19
Keywords
oral microbiota, periodontitis, systemic disease, diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, oral dysbiosis, IL-17, periodontal inflammation, Capnocytophaga, Porphyromonas, Pseudomonas, Prevotella, Selenomonas, Leptotrichia, osteoclastogenesis, periodontal bone loss, leukocyte adhesion deficiency
MeSH terms
Animals, Bacteria, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Mouth, Periodontitis, Periodontium, 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.

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