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ISME J DOI:10.1038/ismej.2014.3

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

Publication TypeJournal Article
Year of Publication2014
AuthorsRooks, MG, Veiga, P, Wardwell-Scott, LH, Tickle, T, Segata, N, Michaud, M, Gallini, CAnn, Beal, C, van Hylckama-Vlieg, JET, Ballal, SA, Morgan, XC, Glickman, JN, Gevers, D, Huttenhower, C, Garrett, WS
JournalISME J
Volume8
Issue7
Pages1403-17
Date Published2014 Jul
ISSN1751-7370
KeywordsAnimals, Anti-Bacterial Agents, Benzoic Acid, Carbohydrate Metabolism, Cell Movement, Colitis, DNA-Binding Proteins, Dopamine, Energy Metabolism, Gastrointestinal Tract, Humans, Inflammation, Inflammatory Bowel Diseases, Mice, Mice, Knockout, Microbiota, Phylogeny, Remission Induction, RNA, Ribosomal, 16S, Signal Transduction, T-Box Domain Proteins
Abstract

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.

URLhttp://dx.doi.org/10.1038/ismej.2014.3
DOI10.1038/ismej.2014.3
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24500617?dopt=Abstract

Alternate JournalISME J
PubMed ID24500617
PubMed Central IDPMC4069400
Grant ListR01CA154426 / CA / NCI NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
K08AI078942 / AI / NIAID NIH HHS / United States
K08 AI078942 / AI / NIAID NIH HHS / United States
P30 DK034854 / DK / NIDDK NIH HHS / United States
T32 AI007638 / AI / NIAID NIH HHS / United States
R01 CA154426 / CA / NCI NIH HHS / United States
R01 HG005969 / HG / NHGRI NIH HHS / United States
5T32AI007638 / AI / NIAID NIH HHS / United States
R01HG005969 / HG / NHGRI NIH HHS / United States
R01 GM099537 / GM / NIGMS NIH HHS / United States