Meta-omics uncover temporal regulation of pathways across oral microbiome genera during in vitro sugar metabolism
Open accessAbstract
Dental caries, one of the most globally widespread infectious diseases, is intimately linked to pH dynamics. In supragingival plaque, after the addition of a carbohydrate source, bacterial metabolism decreases the pH which then subsequently recovers. Molecular mechanisms supporting this important homeostasis are poorly characterized in part due to the fact that there are hundreds of active species in dental plaque. Only a few mechanisms (for example, lactate fermentation, the arginine deiminase system) have been identified and studied in detail. Here, we conducted what is to our knowledge, the first full transcriptome and metabolome analysis of a diverse oral plaque community by using a functionally and taxonomically robust in vitro model system greater than 100 species. Differential gene expression analyses from the complete transcriptome of 14 key community members revealed highly varied regulation of both known and previously unassociated pH-neutralizing pathways as a response to the pH drop. Unique expression and metabolite signatures from 400 detected metabolites were found for each stage along the pH curve suggesting it may be possible to define healthy and diseased states of activity. Importantly, for the maintenance of healthy plaque pH, gene transcription activity of known and previously unrecognized pH-neutralizing pathways was associated with the genera Lactobacillus, Veillonella and Streptococcus during the pH recovery phase. Our in vitro study provides a baseline for defining healthy and disease-like states and highlights the power of moving beyond single and dual species applications to capture key players and their orchestrated metabolic activities within a complex human oral microbiome model.
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The Stephan Response describes the re-establishment of pH homeostasis following pulses of carbohydrate in the oral cavity, in which pathways generating alkali, including those producing arginine, ornithine, citrulline, glutamate, serine, threonine, and urea, are stimulated following glucose intake.
“The Stephan Response describes the re‐establishment of pH homeostasis following pulses of carbohydrate in the oral cavity: in this reaction, pathways generating alkali, including those producing arginine, ornithine, citrulline, glutamate, serine, threonine, and urea, are stimulated following glucose intake.176”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [176]
Lactobacilli are common and robust bacteria in the mouth and gut, able to tolerate low pH and to generate NO in culture.
“At the genus level, Lactobacilli are common and robust bacteria in the mouth and gut, able to tolerate low pH and to generate NO in culture[74,412].”
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 [412]
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- Authors
- Edlund, A., Yang, Y., Yooseph, S., Hall, A. P., Nguyen, D. D., Dorrestein, P. C., Nelson, K. E., He, X., Lux, R., Shi, W., & McLean, J. S.
- Affiliations
- J. Craig Venter Institute (US)
- University of California San Diego (US)
- University of California, Los Angeles (US)
- Corresponding author
- McLean, Jeffrey S
- ORCID
- Venue
- The ISME Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05-29
- Volume
- 9
- Issue
- 12
- Pages
- 2605-2619
- ISSN
- 1751-7362 (ISSN-L)
- 1751-7370
- PMC
- PMC4817640
- OpenAlex
- W2345151741
- Cited by
- 84
- References
- 57
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 12 · 2021: 2 · 2020: 7 · 2019: 10 · 2018: 7 · 2017: 9 · 2016: 13 · 2015: 2
- FWCI
- 13.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The ISME Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (5r01de020102-10, 1R01DE020102)
- University of California, Davis
- National Institute of General Medical Sciences (R01GM095373)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK097154)
- National Institute of Dental and Craniofacial Research (1-R01-DE020102, R01-DE020102, K99DE024543, DE022734, T90 (DE022734) training award, T90DE022734)
- 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 › Periodontics › Dental Health and Care Utilization
- Keywords
- dental caries, oral microbiota, supragingival plaque, pH control, sugar metabolism, bacterial transcriptome, bacterial metabolome, Lactobacillus, Veillonella, Streptococcus, lactic acid fermentation, arginine deiminase system, temporal gene expression
- MeSH terms
- Adult, Bacteria, Dental Caries, Dental Plaque, Female, Humans, Hydrogen-Ion Concentration, Male, Mouth, Carbohydrate Metabolism, Microbiota
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