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

The ISME journal (2014-02-07)
Michelle G Rooks, Patrick Veiga, Leslie H Wardwell-Scott, Timothy Tickle, Nicola Segata, Monia Michaud, Carey Ann Gallini, Chloé Beal, Johan E T van Hylckama-Vlieg, Sonia A Ballal, Xochitl C Morgan, Jonathan N Glickman, Dirk Gevers, Curtis Huttenhower, Wendy S Garrett
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Benzoic acid, ACS reagent, ≥99.5%
Supelco
Benzoic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Melting point standard 121-123°C, analytical standard
Supelco
Metronidazole, analytical standard
Supelco
Mettler-Toledo Calibration substance ME 18555, Benzoic acid, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC)
Sigma-Aldrich
Benzoic acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Metronidazole, BioXtra
Sigma-Aldrich
Benzoic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.9% (alkalimetric)
Supelco
Metronidazole, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Benzoic acid, certified reference material for titrimetry, certified by BAM, ≥99.5%
USP
Benzoic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Benzoic acid, ReagentPlus®, 99%
Sigma-Aldrich
Benzoic acid, meets analytical specification of Ph. Eur., BP, USP, FCC, E210, 99.5-100.5% (alkalimetric)
Supelco
Metronidazole, VETRANAL®, analytical standard
Supelco
Benzoic acid, Standard for quantitative NMR, TraceCERT®
Supelco
Benzoic Acid Solution, certified reference material, 2000 μg/mL in methylene chloride
Sigma-Aldrich
Potassium benzoate, ReagentPlus®, 99%
Sigma-Aldrich
Benzoic acid, natural, ≥99.5%, FCC, FG
Sigma-Aldrich
Benzoic acid, purified by sublimation, ≥99%
Metronidazole, European Pharmacopoeia (EP) Reference Standard
Supelco
SS Benzoic Acid, 2000 μg/mL in dichloromethane, analytical standard
Sigma-Aldrich
Metronidazole, SAJ first grade, ≥99.0%
Sigma-Aldrich
Benzoic acid, SAJ first grade, ≥99.5%
Benzoic acid, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Benzoic acid, SAJ special grade, ≥99.5%