title: Amelioration of DSS-induced murine colitis by VSL#3 supplementation is primarily associated with changes in ileal microbiota composition.
abstract: Inflammatory bowel diseases encompass gastrointestinal illnesses typified by chronic inflammation, loss of epithelial integrity and gastrointestinal microbiota dysbiosis. In an effort to counteract these characteristic perturbations, we used stem cells and/or a probiotic therapy in a murine model of Dextran Sodium Sulfate induced colitis to examine both their efficacy in ameliorating disease and impact on niche-specific microbial communities of the lower GI tract. Colitis was induced in C57BL/6 mice by administering 3% DSS in drinking water for 10 days prior to administering one of three treatment plans: daily probiotic (VSL#3) supplementation for 3 days, a single tail vein injection of 1x10 (6) murine mesenchymal stem cells, or both. Ileal, cecal and colonic sections were collected for microbiota and histological analyses. Microbiota profiling revealed distinct bacterial community compositions in the ileum, cecum and colon of control untreated animals, all of which were predicted in silico to be enriched for a number of discrete KEGG pathways, indicating compositional and functional niche specificity in healthy animals. DSS-treatment perturbed community composition in all three niches with ileal communities exhibiting the greatest change relative to control animals. Each treatment group exhibited treatment-specific alterations in microbiota composition in the lower GI tract, though disease scores were only improved in VSL#3-treated animals. The ileal microbiota were most profoundly altered in composition in this group of animals and characterized by significant Enterobacteriaceae enrichment compared with colitic mice (P<0.05).
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA; These authors contributed equally to this manuscript.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Mar
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA; These authors contributed equally to this manuscript.
authors.forename: Nabeetha A
authors.initials: NA
authors.lastname: Nagalingam
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA; Current address: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Song
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA.
authors.forename: Michio
authors.initials: M
authors.lastname: Onizawa
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification; D058448:Biota / Q000187:drug effects*; D002432:Cecum / Q000382:microbiology / Q000473:pathology; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity*; D004035:Diet Therapy / Q000379:methods*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D006651:Histocytochemistry; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000008:administration & dosage*; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D016264:Dextran Sulfate
keywords: 16S rRNA; DSS; Ileum; Microbiome; Microbiota; Probiotic; Stem Cells; Ulcerative Colitis; VSL#3