Abstract
Microbial dysbiosis is known to play a key role in a variety of complex diseases such as IBD, diabetes, obesity and C. difficile‐associated disease. Little is known regarding the effect of epithelial ion transport processes on the intestinal microbiota. Na+/H+ exchanger isoform 3 (NHE3) plays an integral role in intestinal Na+ absorption and was used to examine region specific microbial dysbiosis. qRT‐PCR revealed that NHE3−/− mice exhibit bacterial overgrowth and microbial dysbiosis in both the lumen and mucosa‐associated bacteria with decreased Firmicutes and increased Bacteriodetes. The genus Bacteroides and the species Bacteroides thetaiotaomicron (B. theta) were significantly increased only in the NHE3−/− terminal ileum where a luminal [Na+] of 43±1 mM was found (WT was 33±3 mM). This correlated with the optimal [Na+] for B. theta growth in vitro,~44 mM Na+. Increased B. theta correlated with increased fut2 mRNA and fucosylation in the NHE3−/− terminal ileum. This study provides a first look at microbial dysbiosis due to altered ion transport. Our data shows the NHE3−/− mice exhibit region specific microbial dysbiosis with changes in B. theta, which correlate with luminal [Na+] and host epithelial changes. These data together show a mechanism for B. theta proliferation and contribution to microbial dysbiosis in the NHE3−/− mouse intestine. Supported by NIH DK079979 to RTW and DK050594 to GES.
Published Version
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