title: Protein relative abundance patterns associated with sucrose-induced dysbiosis are conserved across taxonomically diverse oral microcosm biofilm models of dental caries.
abstract: BACKGROUND
  The etiology of dental caries is multifactorial, but frequent consumption of free sugars, notably sucrose, appears to be a major factor driving the supragingival microbiota in the direction of dysbiosis. Recent 16S rRNA-based studies indicated that caries-associated communities were less diverse than healthy supragingival plaque but still displayed considerable taxonomic diversity between individuals. Metagenomic studies likewise have found that healthy oral sites from different people were broadly similar with respect to gene function, even though there was an extensive individual variation in their taxonomic profiles. That pattern may also extend to dysbiotic communities. In that case, shifts in community-wide protein relative abundance might provide better biomarkers of dysbiosis that can be achieved through taxonomy alone.
  
  
  RESULTS
  In this study, we used a paired oral microcosm biofilm model of dental caries to investigate differences in community composition and protein relative abundance in the presence and absence of sucrose. This approach provided large quantities of protein, which facilitated deep metaproteomic analysis. Community composition was evaluated using 16S rRNA sequencing and metaproteomic approaches. Although taxonomic diversity was reduced by sucrose pulsing, considerable inter-subject variation in community composition remained. By contrast, functional analysis using the SEED ontology found that sucrose induced changes in protein relative abundance patterns for pathways involving glycolysis, lactate production, aciduricity, and ammonia/glutamate metabolism that were conserved across taxonomically diverse dysbiotic oral microcosm biofilm communities.
  
  
  CONCLUSIONS
  Our findings support the concept of using function-based changes in protein relative abundance as indicators of dysbiosis. Our microcosm model cannot replicate all aspects of the oral environment, but the deep level of metaproteomic analysis it allows makes it suitable for discovering which proteins are most consistently abundant during dysbiosis. It then may be possible to define biomarkers that could be used to detect at-risk tooth surfaces before the development of overt carious lesions.
authors.affiliation: Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, 515 Delaware St. SE, Minneapolis, MN, 55455, USA. jrudney@umn.edu.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Rudney
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 321 Church Street SE, Minneapolis, MN, 55455, USA. pjagtap@umn.edu.|Center for Mass Spectrometry and Proteomics, University of Minnesota, 1479 Gortner Avenue, Saint Paul, MN, 55108, USA. pjagtap@umn.edu.
authors.forename: Pratik D
authors.initials: PD
authors.lastname: Jagtap
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, 420 Delaware St. SE, Minneapolis, MN, 55455, USA. cavanr@biostat.umn.edu.
authors.forename: Cavan S
authors.initials: CS
authors.lastname: Reilly
authors.affiliation: Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, 515 Delaware St. SE, Minneapolis, MN, 55455, USA. chenx096@umn.edu.
authors.forename: Ruoqiong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 321 Church Street SE, Minneapolis, MN, 55455, USA. marko025@umn.edu.|Center for Mass Spectrometry and Proteomics, University of Minnesota, 1479 Gortner Avenue, Saint Paul, MN, 55108, USA. marko025@umn.edu.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Markowski
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 321 Church Street SE, Minneapolis, MN, 55455, USA. higgi022@umn.edu.|Center for Mass Spectrometry and Proteomics, University of Minnesota, 1479 Gortner Avenue, Saint Paul, MN, 55108, USA. higgi022@umn.edu.
authors.forename: LeeAnn
authors.initials: L
authors.lastname: Higgins
authors.affiliation: University of Minnesota Supercomputing Institute, 117 Pleasant St. SE, Minneapolis, MN, 55455, USA. jj@msi.umn.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Johnson
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 321 Church Street SE, Minneapolis, MN, 55455, USA. tgriffin@umn.edu.|Center for Mass Spectrometry and Proteomics, University of Minnesota, 1479 Gortner Avenue, Saint Paul, MN, 55108, USA. tgriffin@umn.edu.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Griffin
mesh_terms: D001426:Bacterial Proteins / Q000032:analysis*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D015415:Biomarkers; D003731:Dental Caries / Q000209:etiology / Q000382:microbiology* / Q000517:prevention & control; D003773:Dental Plaque / Q000737:chemistry / Q000382:microbiology*; D064806:Dysbiosis / Q000139:chemically induced* / Q000378:metabolism / Q000382:microbiology; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D059013:Microbial Consortia / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D064307:Microbiota / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000032:analysis*; D040901:Proteomics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012463:Saliva / Q000382:microbiology; D013395:Sucrose / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; D011506:Proteins; D012336:RNA, Ribosomal, 16S; D013395:Sucrose