Intake of low dietary fiber changes microbiota composition and reduces IL-10 production from small intestinal T cells

Abstract

Abstract Regulatory immune responses are crucial for intestinal homeostasis against stimuli like diet and microbiota. The microbiota influences the regulatory immune response by inducing colonic Foxp3+ regulatory T cells and other lymphocytes by metabolizing diet-derived products. For example, fiber-fermenting microbiota process fermentable fiber into metabolites like short-chain-fatty-acids (SCFA) and help activate IL-10-producing T cells. However, studies showed that high-fat (low-fiber) diet alters the abundance of Treg-inducing commensal bacteria promoting intestinal inflammation. Previous studies in our lab showed that low fermentable fiber affects the generation of many intestinal T cells, especially intraepithelial CD4+CD8aa+ T cells (DP IELs) and CD8aa IELs. However, it is still uncertain how dietary fiber affects small intestinal T cell function, including IL-10 production. To address this, we fed IL-10-GFP reporter mice with a regular chow diet or an isocaloric isonitrogenous diet that replaced fiber with non-fermentable fiber (LFF). After four weeks, the lymphocytes and microbiota from the small intestine were analyzed. Our preliminary findings show that IL-10 mRNA expression and IL-10-GFP production from intestinal lymphocytes was lower in mice fed LFF diet when compared to the control. Moreover, 16S RNA sequencing of intestinal contents showed changes in relative frequencies of several OTUs between diets. These results suggests that certain bacterial species affected by the diet could be significant in promoting IL-10 production by small intestinal T cells. Further studies will seek to understand how fiber plays a role in orchestrating the host-microbiota interactions to maintain intestinal tolerance. These studies were conducted at Emory University and funded by the following NIH grants: 1R01DK129950-01 (NIDDK-NIH from LCB); 5T32AI106699-08 (NIDDK-NIH from Antimicrobial Resistance and Therapeutic Discovery Training Program)