Diet induced changes in microbiota composition affect the development of small intestinal T cells over generations

Abstract

Abstract The relationship of microbiota and host is a dynamic and bidirectional process. The microbiota has a strong influence in the development of the host’s immune system, yet the host shapes the composition of the microbiota as well, through the immune response, and importantly, through diet. In the current study we evaluated how modification in the carbohydrate and fiber content of a diet impacts the intestinal immune response. Mice were weaned into a standard natural ingredient diet (Reg) or a purified non-fermentable fiber only diet (NFF) and the immune cell composition was analyzed after four weeks. Animals in the NFF diet had strong changes in their microbiota composition and defects in the development of small intestinal intraepithelial T cells including the lack of CD4+CD8aa+ T cells and TCRab+CD8ab+ T cells. The effect of NFF consumption both in microbiota composition as well as IEL T cell development, was reversible if animals were fed a Reg diet. However, if animals were born from parents fed an NFF diet and kept on NFF diet until weaning, the effect on IEL T cells was non reversible and the offspring of these mice did not develop IEL T cells even if fed a reg diet. Fecal matter transplant from mice fed a Reg diet, together with a Reg diet was able to induce the development of IEL T cells, suggesting the defect observed in the offspring of mice fed a NFF diet is the result of the loss of microbes required for the development of IEL T cells. This study shows how changes in the diet can result in the loss of specific microbiota species over generations that are important for the correct development of the intestinal immune system. Supported by grant from NIH RO1 DK129950-01