title: Meta-omics uncover temporal regulation of pathways across oral microbiome genera during in vitro sugar metabolism.
abstract: 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.
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, La Jolla, CA, USA.|School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Edlund
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, La Jolla, CA, USA.
authors.forename: Youngik
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, La Jolla, CA, USA.
authors.forename: Shibu
authors.initials: S
authors.lastname: Yooseph
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, La Jolla, CA, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Hall
authors.affiliation: Departments of Chemistry and Biochemistry, Pharmacology, and Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Don D
authors.initials: DD
authors.lastname: Nguyen
authors.affiliation: Departments of Chemistry and Biochemistry, Pharmacology, and Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, La Jolla, CA, USA.|Department of Human Genomic Medicine, J. Craig Venter Institute, Rockville, MD, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Nelson
authors.affiliation: School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Xuesong
authors.initials: X
authors.lastname: He
authors.affiliation: School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Renate
authors.initials: R
authors.lastname: Lux
authors.affiliation: School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, La Jolla, CA, USA.|Department of Periodontics, University of Washington, Seattle, WA, USA.
authors.forename: Jeffrey S
authors.identifier: http://orcid.org/0000-0001-9934-5137
authors.initials: JS
authors.lastname: McLean
mesh_terms: D000328:Adult; D001419:Bacteria / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D003731:Dental Caries / Q000382:microbiology; D003773:Dental Plaque / Q000382:microbiology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D064307:Microbiota; D009055:Mouth / Q000737:chemistry / Q000382:microbiology*