Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission

• Published in: The ISME Journal 2014-07, Vol.8 (7), p.1403-1417
• Main Authors: Rooks, Michelle G, Veiga, Patrick, Wardwell-Scott, Leslie H, Tickle, Timothy, Segata, Nicola, Michaud, Monia, Gallini, Carey Ann, Beal, Chloé, van Hylckama-Vlieg, Johan ET, Ballal, Sonia A, Morgan, Xochitl C, Glickman, Jonathan N, Gevers, Dirk, Huttenhower, Curtis, Garrett, Wendy S
• Format: Article
• Language: English
• Subjects: 692/698/2741/2135; 692/699/1503/257/1389; 692/700/565; Animals; Anti-Bacterial Agents - pharmacology; Benzoic Acid - metabolism; Biomedical and Life Sciences; Carbohydrate Metabolism; Cell Movement; Colitis - drug therapy; Colitis - genetics; Colitis - microbiology; Colitis - pathology; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; Dopamine - metabolism; Ecology; Energy Metabolism; Evolutionary Biology; Gastrointestinal Tract - microbiology; Humans; Inflammation - drug therapy; Inflammation - genetics; Inflammation - microbiology; Inflammation - pathology; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - microbiology; Inflammatory Bowel Diseases - pathology; Life Sciences; Mice; Mice, Knockout; Microbial activity; Microbial Ecology; Microbial Genetics and Genomics; Microbiology; Microbiota - drug effects; Microbiota - genetics; Original; original-article; Phylogeny; Remission Induction; RNA, Ribosomal, 16S - classification; RNA, Ribosomal, 16S - genetics; Signal Transduction; T-Box Domain Proteins - deficiency; T-Box Domain Proteins - genetics; Xenobiotics
• ISSN: 1751-7362; 1751-7370
• DOI: 10.1038/ismej.2014.3

Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet −/− Rag2 −/− mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis.