Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission.
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.
Harvard School of Public Health, Boston, MA, USA.
Michelle G
MG
Rooks
1] Harvard School of Public Health, Boston, MA, USA [2] Danone Research, Palaiseau, France.
Patrick
P
Veiga
1] Harvard School of Public Health, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
Leslie H
LH
Wardwell-Scott
Harvard School of Public Health, Boston, MA, USA.
Timothy
T
Tickle
Harvard School of Public Health, Boston, MA, USA.
Nicola
N
Segata
Harvard School of Public Health, Boston, MA, USA.
Monia
M
Michaud
Harvard School of Public Health, Boston, MA, USA.
Carey Ann
CA
Gallini
Danone Research, Palaiseau, France.
Chloé
C
Beal
Danone Research, Palaiseau, France.
Johan E T
JE
van Hylckama-Vlieg
Children's Hospital, Boston, MA, USA.
Sonia A
SA
Ballal
Harvard School of Public Health, Boston, MA, USA.
Xochitl C
XC
Morgan
Harvard Medical School, Boston, MA, USA.
Jonathan N
0000000309102655
JN
Glickman
Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Dirk
D
Gevers
1] Harvard School of Public Health, Boston, MA, USA [2] Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Curtis
C
Huttenhower
1] Harvard School of Public Health, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and MIT, Cambridge, MA, USA [4] Dana-Farber Cancer Institute, Boston, MA, USA.
Wendy S
WS
Garrett
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019817:Benzoic Acid / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002465:Cell Movement; D003092:Colitis / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D004734:Energy Metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000187:drug effects / Q000235:genetics*; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000145:classification / Q000235:genetics; D012074:Remission Induction; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics; D000098815:T-bet Transcription Factor
D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D012336:RNA, Ribosomal, 16S; C499308:Rag2 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D019817:Benzoic Acid; D004298:Dopamine