Effects of dietary fiber on the intestinal humoral immune response via interactions with the microbiota 2260105

Abstract

The Western diet, rich in fats and low in fermentable fibers, has been associated with a range of immune-mediated inflammatory diseases. Dietary fiber is the main energy source for gut bacteria, promoting a rich microbial diversity. We have previously demonstrated that microbiota changes induced by a low-fermentable fiber diet (LFF) impair the development of several intestinal T cell populations. However, the importance of dietary fiber for the intestinal humoral immune system is less understood. Secretory IgA (sIgA) is essential for maintaining gut microbiota homeostasis. Here, we show that sIgA is significantly reduced in the small intestinal and fecal contents of mice fed a low fiber diet compared to mice fed a standard chow (SC). IgA secretion by PC is not impaired, as shown by ELISA of culture media from sorted IgA+ PC from SC and LFF-fed mice. However, flow cytometry and ELISpot assays revealed that low IgA levels are due to a reduction in numbers of small intestinal lamina propria IgA+ PC in LFF-fed mice, while other isotypes are not affected. Using T cell deficient mice, we demonstrate that LFF diet reduces T-dependent, but not T-independent, sIgA. Future studies will elucidate how changes in the microbiota and dietary fiber result in the loss of IgA+ PCs. To this end, time-stamping of PC will allow to track survival and turnover rate in LFF and control mice. These results provide insight into the interactions between fiber, the microbiota, and B cell responses, and further our understanding on how diet modulates the mucosal immune response. 5R01DK129950 Mucosal and Regional Immunology (MUC)