The DOI matches its Crossref record, with a small difference in title or year; 65 of the 65 references it cites were found in a registry or an index.
Oral Microbiome Metabolism: From “Who Are They?” to “What Are They Doing?”
Abstract
Recent advances in molecular biology have facilitated analyses of the oral microbiome (“Who are they?”); however, its functions (e.g., metabolic activities) are poorly understood (“What are they doing?”). This review aims to summarize our current understanding of the metabolism of the oral microbiome. Saccharolytic bacteria—including Streptococcus, Actinomyces, and Lactobacillus species—degrade carbohydrates into organic acids via the Embden-Meyerhof-Parnas pathway and several of its branch pathways, resulting in dental caries, while alkalization and acid neutralization via the arginine deiminase system, urease, and so on, counteract acidification. Proteolytic/amino acid–degrading bacteria, including Prevotella and Porphyromonas species, break down proteins and peptides into amino acids and degrade them further via specific pathways to produce short-chain fatty acids, ammonia, sulfur compounds, and indole/skatole, which act as virulent and modifying factors in periodontitis and oral malodor. Furthermore, it is suggested that ethanol-derived acetaldehyde can cause oral cancer, while nitrate-derived nitrite can aid caries prevention and systemic health. Microbial metabolic activity is influenced by the oral environment; however, it can also modify the oral environment, enhance the pathogenicity of bacteria, and induce microbial selection to create more pathogenic microbiome. Taking a metabolomic approach to analyzing the oral microbiome is crucial to improving our understanding of the functions of the oral microbiome.
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In the citing paper
“These bacteria can cause demineralization of dental enamel and development of carious lesions, and on the other hand, promote bacterial acidogenicity and acidification by increasing cell membrane permeability to protons, induction of H+- ATPase activity, and stimulation of metabolic pathways involved in acid neutralization and alkalinization [83].”
From A Cross-Talk between Diet and the Oral Microbiome: Balance of Nutrition on Inflammation and Immune System’s Response during Periodontitis (2022) · cites this paper as [83]
In the citing paper
“They are broken down into peptides and amino acids (aspartate, serine, and cysteine) through the action of host proteases and peptidases [83].”
From A Cross-Talk between Diet and the Oral Microbiome: Balance of Nutrition on Inflammation and Immune System’s Response during Periodontitis (2022) · cites this paper as [83]
In the citing paper
“However, the degradation of protein substrates plays an important role in the pathogenesis of the periodontal disease [83].”
From A Cross-Talk between Diet and the Oral Microbiome: Balance of Nutrition on Inflammation and Immune System’s Response during Periodontitis (2022) · cites this paper as [83]
In the citing paper
“Fermentation of amino acids neutralizes acidic environments, creating a more favorable atmosphere for the growth of other periodontitis’ pathogens [83].”
From A Cross-Talk between Diet and the Oral Microbiome: Balance of Nutrition on Inflammation and Immune System’s Response during Periodontitis (2022) · cites this paper as [83]
In the citing paper
“Amino acids are fermented to generate short-chain fatty acids, such as propionate, butyrate, succinate, acetate, and formate [83].”
From A Cross-Talk between Diet and the Oral Microbiome: Balance of Nutrition on Inflammation and Immune System’s Response during Periodontitis (2022) · cites this paper as [83]
In the citing paper
“The increased depth of the gingival pocket and the increased production of gingival crevicular fluid induces an increase in bacteria involved in protein degradation.”
From A Cross-Talk between Diet and the Oral Microbiome: Balance of Nutrition on Inflammation and Immune System’s Response during Periodontitis (2022) · cites this paper as [83]
In the citing paper
“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”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“Moreover, processed carbohydrate consumption has been associated with increased incidence of periodontal disease.8, 24, 26, 181, 188, 251”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“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.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“Such processes encourage the outgrowth of acidogenic bacteria, such as S mutans, lactobacilli, and bifidobacteria that enhance the carcinogenicity of dental plaque.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“Pathways in which sugar is metabolized are also shared among some periodontal pathogens, such as Fusobacterium and Prevotella, which can likewise cause acidification.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“During the development of periodontal disease, protein‐rich and neutral‐alkaline environmental pressures promote the outgrowth of periodontal pathogens.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“Inflammatory processes promote the outgrowth of inflammophilic bacteria via the production of proteinaceous substrates resulting from tissue destruction.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“Amino acids are fermented to produce short‐chain fatty acids, such as propionate, butyrate, succinate, acetate, and formate.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“Amino acid fermentation neutralizes acidic environments, making the environment more favorable for outgrowth of additional periodontitis‐associated pathogens.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“Deepening of the gingival crevice and increased production of gingival crevicular fluid increases the relative abundance of protein‐degrading bacteria.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [8]
In the citing paper
“For instance, saccharolytic (sugar metabolizing) bacteria such as Streptococcus and Lactobacillus have been associated with dental caries, while proteolytic (protein metabolizing) bacteria such as Prevotella and Porphyromonas have been associated with periodontitis and halitosis[183].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [183]
In the citing paper
“Yet, individual bacteria do not act in a vacuum, but rather function in interdependent microbial communities whose conglomerate activity can impact oral and systemic health[183,188,189].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [183]
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“Takahashi et al. succinctly describe the emerging trend of the metabolomic study of oral biofilms and microbiomes as less of “who are they?” and more of “what are they doing?” which summarizes the aims that we have succeeded in investigating in this study (Takahashi et al., 2012; Takahashi, 2015).”
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“Research (Takahashi 2015) has demonstrated that oral microbiota influences host physiology primarily through the production of small molecular compounds that circulate throughout host tissues, participating in various local and systemic metabolic processes.”
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Increase in the level of oral neutrophils with gingival inflammation – A population survey
Sreenivasan, P. K., & Prasad, K. V. V. (2022) · The Saudi Dental Journal · doi:10.1016/j.sdentj.2022.11.004 · Cited by 10
“…available evidence, informational programs, and outreach utilizing various educational channels to engage and implement adequate oral hygiene measures, common oral diseases remain prevalent (Arweiler et al., 2018, Chapple et al., 2015, Lindenmuller and Lambrecht 2011, Twetman 2018, Takahashi 2015).”
Kommerein, N., Vierengel, N., Groß, J., Opatz, T., Al‐Nawas, B., & Müller-Heupt, L. K. (2022) · Microorganisms · doi:10.3390/microorganisms10050965 · Cited by 11
Metabolic differences of the oral microbiome related to dental caries – A pilot study
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Bacterial Virulence Factors that Contribute to Periodontal Pathogenesis
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“These disturbances in biofilm ecology can lead to dysbiosis, increasing the risk of oral diseases such as dental caries and periodontal diseases [2,3].”
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Research Status of Silver Nanoparticles for Dental Applications
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“S. mutans are recognized as the main bacteria in cariogenic biofilms responsible for secondary caries [66,67], which are an important factor affecting the life of resin composites.”
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Alessandri, G., Fontana, F., Mancabelli, L., Tarracchini, C., Lugli, G. A., Argentini, C., Longhi, G., Rizzo, S. M., Vergna, L. M., Anzalone, R., et al. (2024) · FEMS Microbiology Ecology · doi:10.1093/femsec/fiae082 · Cited by 9
Plaza‐Díaz, J., Ruiz‐Ojeda, F. J., Plaza, B. L., Brandimonte‐Hernández, M., Álvarez‐Mercado, A. I., Arcos-Castellanos, L., Feliú, J., Hummel, T. R., Milla, S. P., & Gil, Á. (2024) · Cancers · doi:10.3390/cancers16193414 · Cited by 8
Microbiome Signatures and Dysbiotic Patterns in Oral Cancer and Precancerous Lesions
Yang, C., Washio, J., Lin, Y., Hsu, M., Wang, D., Tsai, F., Lin, Y., Tu, H., Chang, H., & Takahashi, N. (2025) · Oral Diseases · doi:10.1111/odi.15317 · Cited by 8
“As summarized in Table S1, these OSCC-associated bacteria, such as Peptostreptococcus , Fusobacterium , Oribacterium , and Catonella , are mostly amino- acid-degrading anaerobes (Takahashi 2015; Washio et al. 2016), previously identified as periodontal or endodontic pathogens.”
Self-citationArishi, R. A., Cheema, A. S., Lai, C. T., Payne, M. S., Geddes, D. T., & Stinson, L. F. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1534750 · Cited by 8
“This dietary change increases the availability of polysaccharides, favoring the growth of taxa that ef fi ciently utilize these complex carbohydrates (Takahashi, 2015).”
Wu, S., Ye, X., Wang, J., Li, M., Fu, Y., & Wang, S. (2026) · Neoplasia · doi:10.1016/j.neo.2026.101290 · Cited by 11
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Oral Microbiome: Potential Link to Systemic Diseases and Oral Cancer
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“subgingival bacterial biofilm is left undisrupted for extended time periods, which allows its colonization with highly pathogenic bacteria [3].”
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“…is limited, and in vitro studies have only found minimal contributions by certain oral bacteria in isolation (Cogo et al., 2008; Sun et al., 2016); it is possible that a larger role is played by oral bacteria within larger, more metabolically active communities, e.g. biofilms (Takahashi, 2015).”
BackgroundMartini, D., Galli, C., Guareschi, C., Angelino, D., Bedogni, G., Biasini, B., Zavaroni, I., Pruneti, C. A., Ventura, M., Galli, D., et al. (2018) · NFS Journal · doi:10.1016/j.nfs.2017.12.001 · Cited by 8
Meal Regularity Plays a Role in Shaping the Saliva Microbiota
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“Oral Prevotella, such as P. intermedia, P. oralis, and P. gingivalis (Nadkarni et al., 2012) are known for degrading proteins and peptides into amino acids (Takahashi, 2015).”
BackgroundCharacterization of polymicrobial biofilms obtained from saliva or carious lesions in dentin
de Farias, A. L., de Carvalho, L. P. F., Méndez, D. A. C., Cruvinel, T., & Brighenti, F. L. (2020) · Biofouling · doi:10.1080/08927014.2020.1826454 · Cited by 8
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The role of aryl hydrocarbon receptor in the occurrence and development of periodontitis
Wu, L., Li, X., Li, J., Wang, Y., Yang, C., Zhao, C., & Gao, L. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1494570 · Cited by 7
“Various oral pathogens have been proven to have the ability to metabolize Trp, leading to the production of indole and its derivatives (20).”
Adams, S., Cawley, A., Arnold, D. S., Hoptroff, M., Slomka, V., Matheson, J. R., Marriott, R. E., Gemmell, M. R., & Marsh, P. D. (2025) · Scientific Reports · doi:10.1038/s41598-025-92545-0 · Cited by 10
Nitrate supplementation affects taste by changing the oral metabolome and microbiome
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Structure, variation and assembly of body‐wide microbiomes in endangered crested ibisNipponia nippon
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“…& Wilmes, 2018); the skin microbiome is essential in lipid metabolism and resistance to transient organisms (Grice, 2015; Scharschmidt & Fischbach, 2013); and the oral microbiome helps transport nutrients to the gut by degradation, alkalization and acid neutralization (Takahashi, 2015).”
BackgroundYamamoto, Y., Washio, J., Shimizu, K., & Takahashi, N. (2024) · Caries Research · doi:10.1159/000540017 · Cited by 8
Self-citationAnticaries activity of egg ovalbumin in an experimental caries biofilm model on enamel and dentin
Giacaman, R. A., Jobet-Vila, P., & Muñoz‐Sandoval, C. (2018) · Clinical Oral Investigations · doi:10.1007/s00784-018-2769-3 · Cited by 7
Dependency of hydration and growth conditions on the mechanical properties of oral biofilms
Pattem, J. K., Davrandi, M., Aguayo, S. D., Ślak, B., Maev, R. G., Allan, E., Spratt, D. A., & Bozec, L. (2021) · Scientific Reports · doi:10.1038/s41598-021-95701-4 · Cited by 7
Distinct Agents Induce Streptococcus mutans Cells with Altered Biofilm Formation Capacity
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Oral Bacterial Acid–Base Metabolism in Caries Screening: A Proof-Of-Concept Study
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The Submucosal Microbiome Correlates with Peri-implantitis Severity
Joshi, A. A., Szafrański, S. P., Steglich, M., Yang, I., Behrens, W., Schaefer-Dreyer, P., Grischke, J., Häußler, S., & Stiesch, M. (2025) · Journal of Dental Research · doi:10.1177/00220345251352809 · Cited by 6
“Utilization of galactose (Takahashi 2015) present on the surfaces of host proteins appeared to be an important adaptation in periodontopathogens to the early peri-implantitis environment, while the production of proteolytic activities potentially capable of degrading host-derived glycoproteins and…”
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Tongue coating metabolic profiles of intra‐oral halitosis patients
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The Role of Periodontopathogens and Oral Microbiome in the Progression of Oral Cancer. A Review
Beltran, J. F., Viafara-García, S. M., Labrador, A. P., & Basterrechea, J. (2021) · The Open Dentistry Journal · doi:10.2174/1874210602115010367 · Cited by 5
Proteomic response in Streptococcus gordonii DL1 biofilm cells during attachment to salivary MUC5B
Robertsson, C., Svensäter, G., Blum, Z., Jakobsson, M. E., & Wickström, C. (2021) · Journal of Oral Microbiology · doi:10.1080/20002297.2021.1967636 · Cited by 6
Relationship between Saliva and Sublingual Immunotherapy
Oka, A., & Okano, M. (2021) · Pathogens · doi:10.3390/pathogens10111358 · Cited by 6
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Metadata
- Authors
- Takahashi, N.
- Affiliations
- Tohoku University (JP)
- Corresponding author
- Takahashi, N.
- ORCID
- Takahashi, N.
- Venue
- Journal of Dental Research
- Publisher
- SAGE Publications
- Published
- 2015-09-16
- Volume
- 94
- Issue
- 12
- Pages
- 1628-1637
- ISSN
- 0022-0345 (ISSN-L)
- 1544-0591
- OpenAlex
- W2177799539
- Semantic Scholar
- 07829a891f6241d91d38c3b9b26b4c8d9c2bf4a9
- Cited by
- 488
- References
- 65
- Citations by year
- 2026: 45 · 2025: 65 · 2024: 49 · 2023: 49 · 2022: 55 · 2021: 50 · 2020: 43 · 2019: 48 · 2018: 27 · 2017: 38 · 2016: 16 · 2015: 2
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Dental Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (26293439)
- 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 Health and Care Utilization
- Keywords
- oral microbiota, microbial metabolism, dental caries, periodontitis, halitosis, arginine deiminase system, urease, short-chain fatty acids, acetaldehyde, nitrite, Streptococcus, Lactobacillus, Porphyromonas, Prevotella, glycolysis, microbial metabolomics
- MeSH terms
- Bacteria, Dental Caries, Dental Plaque, Humans, Mouth, Oral Health, Periodontal Diseases, Microbiota
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