Effects of dietary fiber on the intestinal humoral immune system via interactions with the microbiota 2959

Abstract Description The Western diet, rich in fats and low in fermentable fibers, has been associated with chronic diseases such as obesity, and a range of immune-mediated inflammatory diseases. Dietary fiber is used by gut bacteria, allowing for a rich microbial diversity. We have previously demonstrated that a low-fiber diet (LFF) leads to changes in the microbiota and thereby impairs the development of several intestinal T cell populations. However, changes in B and plasma cells (PC), and mechanisms by which fiber affects the intestinal humoral immune system have yet to be elucidated. Secretory IgA (sIgA) is essential for maintaining gut microbiome homeostasis. We hypothesize that diet-driven alterations to the gut microbiota affect IgA-producing PC development and function. Here, we show that sIgA is significantly reduced in the small intestinal content and feces of mice fed LFF diet compared to mice fed a standard chow (SC). Flow cytometry and ELISpot assays revealed that this reduction is due to a lower number of small intestinal lamina propria IgA+ PC in LFF-fed mice, while other isotypes are not impacted by diet. Secretion of sIgA per PC is not impaired, as shown by ELISA of culture media from sorted IgA+ PC from SC and LFF-fed mice. IgA-seq analysis will determine if LFF diet affects IgA coating of bacteria, and sequencing analysis will investigate changes in the IgA repertoire. These results provide insight into the interactions between fiber, microbiome, and the B cell response. Funding Sources Supported by NIDDK 5R01DK129950-02 Topic Categories Mucosal and Regional Immunology (MUC)