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TNF Modulates The Gut Microbiota And Drives Inflammation
Author(s) -
Kozik Ariangela,
JonesHall Yava,
Nakatsu Cindy
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.142.8
Subject(s) - tumor necrosis factor alpha , gut flora , inflammatory bowel disease , colitis , inflammation , ulcerative colitis , immunology , microbiome , feces , disease , crohn's disease , medicine , biology , microbiology and biotechnology , bioinformatics
Inflammatory Bowel Disease (IBD) consists of Ulcerative Colitis and Crohn's Disease (CD). The etiology remains unclear; however tumor necrosis factor (TNF) is known to promote the inflammation seen in these diseases. Many patients with IBD have elevated systemic and local levels of TNF and are treated with anti‐TNF drugs with variable success. It is also clear that the gut microbiota play a role in the development and perpetuation of IBD. We hypothesize that TNF modulates the gut microflora and that the severity of colitis correlates with specific microbiota shifts. To address our hypothesis, we examined the gut microbiota in mouse models of acute and chronic Trinitrobenzenesulfonic acid (TNBS) induced colitis in the presence (Wildtype, WT) and absence of TNF (TNF KO). Mice were given 1intra‐rectal (IR) injection (acute) TNBS. Feces were collected for DNA extraction and microbiome analyses. TNBS treated WT mice had more inflammation than TNBS treated TNF KOmice, proving that TNF drives inflammation in the acute model. Analyses of the fecal microbial communities at both days 0 and 10 revealed significant,Tnf‐dependent, differences in alpha and beta diversity, as well as notable differences in many species that were also primarily Tnf‐dependent. The results of the microbial analyses coupled with the results of the pathology support our hypothesis that TNF modulates the gut microbiota, which contributes to the severity of acute colitis. Analyses of the chronic studies are ongoing. We expect to see similar inflammatory results WT and TNF KOmice, with the potential for additional shifts in the microbiota as disease progresses from acute to chronic.