title: The colitis-associated transcriptional profile of commensal Bacteroides thetaiotaomicron enhances adaptive immune responses to a bacterial antigen.
abstract: BACKGROUND
  Inflammatory bowel diseases (IBD) may be caused in part by aberrant immune responses to commensal intestinal microbes including the well-characterized anaerobic gut commensal Bacteroides thetaiotaomicron (B. theta). Healthy, germ-free HLA-B27 transgenic (Tg) rats develop chronic colitis when colonized with complex gut commensal bacteria whereas non-transgenic (nTg) rats remain disease-free. However, the role of B. theta in causing disease in Tg rats is unknown nor is much known about how gut microbes respond to host inflammation.
  
  
  METHODS
  Tg and nTg rats were monoassociated with a human isolate of B. theta. Colonic inflammation was assessed by histologic scoring and tissue pro-inflammatory cytokine measurement. Whole genome transcriptional profiling of B. theta recovered from ceca was performed using custom GeneChips and data analyzed using dChip, Significance Analysis of Microarrays, and Gene Set Enrichment Analysis (GSEA) software. Western Blots were used to determine adaptive immune responses to a differentially expressed B. theta gene.
  
  
  RESULTS
  B. theta monoassociated Tg rats, but not nTg or germ-free controls, developed chronic colitis. Transcriptional profiles of cecal B. theta were significantly different in Tg vs. nTg rats. GSEA revealed that genes in KEGG canonical pathways involved in bacterial growth and metabolism were downregulated in B. theta from Tg rats with colitis though luminal bacterial concentrations were unaffected. Bacterial genes in the Gene Ontology molecular function "receptor activity", most of which encode nutrient binding proteins, were significantly upregulated in B. theta from Tg rats and include a SusC homolog that induces adaptive immune responses in Tg rats.
  
  
  CONCLUSIONS
  B. theta induces colitis in HLA-B27 Tg rats, which is associated with regulation of bacterial genes in metabolic and nutrient binding pathways that may affect host immune responses. These studies of the host-microbial dialogue may lead to the identification of novel microbial targets for IBD therapies.
authors.affiliation: Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America. jjhansen@med.unc.edu
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Hansen
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Peterson
authors.forename: Laura
authors.initials: L
authors.lastname: Goeser
authors.forename: Ting-Jia
authors.initials: TJ
authors.lastname: Fan
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism; D001439:Bacteroides / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D003092:Colitis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D050296:Microbial Viability / Q000235:genetics; D051381:Rats; D055647:Rats, Transgenic; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic; D059467:Transcriptome; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D015796:HLA-B27 Antigen; D018836:Inflammation Mediators; D008565:Membrane Proteins; C057616:tonB protein, Bacteria