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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Additional file 1 of Profiling the Salivary microbiome of the Qatari population
Murugesan, S., Ahmad, S. F. A., Singh, P., Saadaoui, M., Kumar, M., & Khodor, S. A. (2020) · Figshare · doi:10.6084/m9.figshare.11984508
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Additional file 4 of Profiling the Salivary microbiome of the Qatari population
Murugesan, S., Ahmad, S. F. A., Singh, P., Saadaoui, M., Kumar, M., & Khodor, S. A. (2020) · Figshare · doi:10.6084/m9.figshare.11984526
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Additional file 2 of Profiling the Salivary microbiome of the Qatari population
Murugesan, S., Ahmad, S. F. A., Singh, P., Saadaoui, M., Kumar, M., & Khodor, S. A. (2020) · Figshare · doi:10.6084/m9.figshare.11984511
Additional file 3 of Profiling the Salivary microbiome of the Qatari population
Murugesan, S., Ahmad, S. F. A., Singh, P., Saadaoui, M., Kumar, M., & Khodor, S. A. (2020) · Figshare · doi:10.6084/m9.figshare.11984520
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“Carbohydrate excess promotes the growth of saccharolytic and acidogenic bacteria such as Streptococcus , Actinomyces , and Veillonella , and has been associated with enamel dem-ineralization and caries formation in the prior literature [14,44–46].”
Fanghong, L. I. U., Xue, H., JIANG, Y., Shaoyong, C. H. E. N., ZHANG, Y., Yu, J., Yu, Q. I. N., Dong, X., Ou, Y., & Qiu, R. (2026) · Journal of Oral Microbiology · doi:10.1080/20002297.2026.2682471
Dysbiosis of oral bacteriome and mycobiome associated with the severity of heart failure
Li, H.-Y., Wu, Q.-Y., Wang, Z.-Y., Hu, X.-M., & Zhang, S.-Y. (2026) · BMC Oral Health · doi:10.1186/s12903-026-08977-1
Oral Microbiota and Flavour Perception
Cuenca, M., Schwartz, M., Corda, M., Heydel, J., Canon, F., Gandía, M., Cilla, A., Gamero, A., & Neiers, F. (2026) · doi:10.1002/9781394293346.ch5
Braga, A. S., Figueira, L. G. T., Kim, R. R., Vertuan, M., Esteves‐Oliveira, M., & Magalhães, A. C. (2026) · Journal of Dentistry · doi:10.1016/j.jdent.2026.106879
Metagenomic analysis of tongue samples from healthy subjects identifies distinct microbiome orotypes
Al-Maweri, S., Ba-Hattab, R., Alomairi, A., Syed, A., Azouni, K. G., Batta, N., Almeer, F., Assad, R., Al-Mansoori, A., Eltai, N. O., et al. (2026) · Journal of Oral Microbiology · doi:10.1080/20002297.2026.2687934
The Mechanism and Pathways of Formation and Modification of Salivary Metabolic Profile in Cancer
Dyachenko, E. I., & Bel’skaya, L. V. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48070728
“It depends on plasma composition, glandular secretion, ductal epithelial transport, and, especially, the rate of salivary flow [18–23].”
Beyond Acidification: Microbial Lactate in the Oral Microbiome–Host Axis
Takahashi, N. (2026) · Journal of Dental Research · doi:10.1177/00220345261462879
“2) (Takahashi et al 2010; Takahashi 2015).”
Self-citationAlteration of subgingival microbiome in patients with type 2 diabetes induced by diabetes treatment
Inoue, M., Sakanaka, A., Katakami, N., Nishizawa, H., Omori, K., Taya, N., Ishikawa, A., Mayumi, S., Takeuchi, H., Amano, A., et al. (2026) · Journal of Diabetes Investigation · doi:10.1111/jdi.70408
“Subgingival bacteria, including Fusobacterium , Prevotella , and Porphyromonas , can degrade and ferment amino acids to produce energy 17,45 .”
Cirio, S., Mantegazza, G., Salerno, C., Guglielmetti, S., Allam, A., Campus, G., & Cagetti, M. G. (2026) · Nutrients · doi:10.3390/nu18162735
“These findings should not be considered confirmatory evidence, but they provide a biologically plausible ecological framework that may help explain the observed reduction in H 2 S concentrations and support future hypothesis-driven investigations [38,39].”
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Guo, T., Chen, Y., Yu, Y., Shao, Y., Wang, C., Li, X., Zhang, H., Xu, C., Cheung, Y., Chen, F., et al. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1903972
“…metabolites may modulate immunity via AhR signaling (Rothhammer and Quintana, 2019; Li et al., 2025; Cheng et al., 2026); and SCFA-related effects are largely extrapolated from gut studies and may involve HDAC inhibition (Takahashi, 2015; Koh et al., 2016; Parada Venegas et al., 2019).”
Elaoulabine, Y., Chelh, T. C., Haddou, S., Ezzaitouni, M., García-Cervantes, A. M., & Guil‐Guerrero, J. L. (2026) · Hygiene · doi:10.3390/hygiene6030064
Liu, X., Meng, L., Song, W., Wang, P., Liu, B., Liu, S., He, Q., Sun, B., Li, W., Guan, Z., et al. (2026) · Open Research (University of Surrey) · doi:10.1002/viw2.70212
Peng, X., Peng, W., Zou, Y., & Li, Z. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1941478
“Prevotella pallens , as a common symbiotic bacterium in the healthy oral microbiome, can produce SCFAs such as propionic acid by fermenting dietary fi ber, exerting anti-in fl ammatory effects and improving host metabolic health (Han and Wang, 2026).”
InfluentialMass Spectrometry-Based Oral Meta-Omics Analysis—What We Know and What We Don’t
Chirițoiu, G. N., Chiritoiu‐Butnaru, M., Porosencova, T., Porosencov, E., Uncuța, D., Istrati, D., Isvoranu, G., Petrescu, A., & Munteanu, C. V. A. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-29437-1_25
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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