title: Probiotic bacteria produce conjugated linoleic acid locally in the gut that targets macrophage PPAR γ to suppress colitis.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) therapies are modestly successful and associated with significant side effects. Thus, the investigation of novel approaches to prevent colitis is important. Probiotic bacteria can produce immunoregulatory metabolites in vitro such as conjugated linoleic acid (CLA), a polyunsaturated fatty acid with potent anti-inflammatory effects. This study aimed to investigate the cellular and molecular mechanisms underlying the anti-inflammatory efficacy of probiotic bacteria using a mouse model of colitis.
  
  
  RESULTS
  The immune modulatory mechanisms of VSL#3 probiotic bacteria and CLA were investigated in a mouse model of DSS colitis. Colonic specimens were collected for histopathology, gene expression and flow cytometry analyses. Immune cell subsets in the mesenteric lymph nodes (MLN), spleen, blood and colonic lamina propria cells were phenotypically and functionally characterized. Fecal samples and colonic contents were collected to determine the effect of VSL#3 and CLA on gut microbial diversity and CLA production. CLA and VSL#3 treatment ameliorated colitis and decreased colonic bacterial diversity, a finding that correlated with decreased gut pathology. Colonic CLA concentrations were increased in response to probiotic bacterial treatment, but without systemic distribution in blood. VSL#3 and CLA decreased macrophage accumulation in the MLN of mice with DSS colitis. The loss of PPAR γ in myeloid cells abrogated the protective effect of probiotic bacteria and CLA in mice with DSS colitis.
  
  
  CONCLUSIONS
  Probiotic bacteria modulate gut microbial diversity and favor local production of CLA in the colon that targets myeloid cell PPAR γ to suppress colitis.
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America. jbassaga@vt.edu
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.forename: Monica
authors.initials: M
authors.lastname: Viladomiu
authors.forename: Mireia
authors.initials: M
authors.lastname: Pedragosa
authors.forename: Claudio
authors.initials: C
authors.lastname: De Simone
authors.forename: Adria
authors.initials: A
authors.lastname: Carbo
authors.forename: Rustem
authors.initials: R
authors.lastname: Shaykhutdinov
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Arthur
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Corl
authors.forename: Hans
authors.initials: H
authors.lastname: Vogel
authors.forename: Martin
authors.initials: M
authors.lastname: Storr
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D044822:Biodiversity; D003092:Colitis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism*; D019936:Probiotics / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; D020011:Protective Agents; D016264:Dextran Sulfate