Industrialized Gut Microbiota Promote Intestinal Inflammation in Mice

Immigration to a highly industrialized nation has been associated with metabolic disease and simultaneous shifts in microbiota composition, but the underlying mechanisms are challenging to test in human studies. Here, we assessed the differential effects of human gut microbiota collected from the United States (US) and rural Thailand on the murine gut mucosa and immune system. Colonization of germ-free mice with microbiota from US individuals resulted in an increased accumulation of innate-like CD8 T cells in the small intestine lamina propria and intra-epithelial compartments when compared to colonization with microbiota from Thai individuals. Both TCRgd and CD8aa T cells showed marked increase in mice receiving the Western microbiota and, interestingly this phenotype was also associated with an increase in intestinal mucus thickness. Serendipitously, an accidentally infected group of mice corroborated this association between elevated inflammatory response and increased mucus thickness. These results suggest that Western-associated human gut microbes contribute to a pro-inflammatory immune response.