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Sex, Age, and TNF Influence the Gut Microbiota in a Mouse Model of TNBS Colitis
Author(s) -
Kozik Ariangela J
Publication year - 2017
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.31.1_supplement.657.12
Subject(s) - microbiome , colitis , biology , gut flora , inflammatory bowel disease , feces , immunology , metagenomics , roseburia , tumor necrosis factor alpha , physiology , disease , microbiology and biotechnology , medicine , lactobacillus , genetics , gene , bacteria
Studies of Crohn's Disease, a subtype of Inflammatory Bowel Disease (IBD), have suggested that the gut microbiota plays a pivotal role in disease development and perpetuation. However, data pertaining to mouse colitis and the gut microbiome are not always consistent or reproducible. It is thought that the variation in the ‘normal’ gut microbiota of humans and animals can be attributed to various host genetic and environmental factors. Several studies have shown that facilities, social stress, differences in handling, and diet have a direct impact on the mouse gut microbiome. However, the impact of sex and age on the microbiome of several commonly used strains of mice has not been well described. We hypothesize that mouse sex and age contribute significantly to differences in the gut microbiome and variation of the response to colitis. To address our hypothesis, we examined the gut microbiota of male and female wildtype (WT) and tumor necrosis factor (TNF) deficient (Tnf −/− ) mice aged 4 weeks to 9 weeks, prior to and after the induction of acute trinitrobenzenesulfonic acid (TNBS) induced colitis. Fecal 16S rRNA gene microbial community sequence analysis pre and post colitis revealed statistically significant sex and age related differences in microbial diversity and composition. The Chao1 diversity metric estimating taxa richness (number different microbes present) within a community revealed that male mice had a lower Chao1 measure than female mice. Both WT and Tnf −/− mice also exhibited sex and age‐based differences in the gut microbiome composition. Male WT mice had higher relative proportions of Ruminococcus and Roseburia spp., while female WT mice had higher proportions of Peptostreptococcaceae. Male Tnf −/− mice had more Streptococcus , while female Tnf −/− mice had more Turicibacter and Clostridiaceae. We were also able to identify several taxa that are differentially abundant between 4, 6, 8, and 9 week old mice. Four week old WT mice had higher relative proportions of Lactobacillus and Proteobacteria while Tnf −/− mice had more Clostridiales and Firmicutes. Six and eight week WT mice had more Firmicutes, while Tnf −/− mice had more Clostridia . The gut microbiota of male and female mice also responded differently to acute TNBS colitis. Male WT mice developed more severe colitis than female WT mice and Tnf −/− mice of both sexes. Canonical Correspondence Analysis (CCA) also confirmed that sex and age, along with TNF, contribute significantly to variation in the mouse gut microbiome. The results of the microbial analyses and histopathological analyses support our hypothesis that sex and age influence the murine gut microbiota, and impacts the severity of acute colitis. It is crucial to consider these factors when using mouse models to study IBD, especially when these studies involve the microbiome.