Deficiency of Dietary Fiber in Slc5a8-Null Mice Promotes Bacterial Dysbiosis and Alters Colonic Epithelial Transcriptome towards Proinflammatory Milieu.

Abstract

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the intestinal tract due to disruption of the symbiotic relationship between the host immune system and microbiota. Various factors alter the gut microbiota which lead to dysbiosis; in particular, diet and dietary fibers constitute important determinants. Dietary fiber protects against IBD; bacteria ferment these dietary fibers in colon and generate short-chain fatty acids (SCFAs), which mediate the anti-inflammatory actions of dietary fibers. SLC5A8 is a high-affinity transporter in the apical membrane of colonic epithelium which mediates the entry of SCFAs from the lumen into cells in Na+-coupled manner. Due to the unique transport kinetics, the function of the transporter becomes important only under conditions of low dietary fiber intake. Here, we have examined the impact of dietary fiber deficiency on luminal microbial composition and transcriptomic profile in colonic epithelium in wild-type (WT) and Slc5a8-null (KO) mice. We fed WT and KO mice with fiber-containing diet (FC-diet) or fiber-free diet (FF-diet) and analyzed the luminal bacterial composition by sequencing 16S rRNA gene in feces. Interestingly, results showed significant differences in the microbial community depending on dietary fiber content and on the presence or absence of Slc5a8. There were also marked differences in the transcriptomic profile of the colonic epithelium depending on the dietary fiber content and on the presence or absence of Slc5a8. We conclude that absence of fiber in diet in KO mice causes bacterial dysbiosis and alters gene expression in the colon that is conducive for inflammation.