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Abstract

The gut microbiota is influenced by numerous environmental and lifestyle factors, with diet being among the most significant. Dietary fiber, also referred to as microbiota-accessible carbohydrates (MACs), plays a crucial role in maintaining microbial diversity, however Western diets typically contain insufficient MAC levels, therefore contributing to reduced microbial richness. In addition, Western diets are rich in ultra-processed foods (UPFs). Despite the health implications of low-MAC diets with high levels of UPFs, gut microbiome research remains largely centered on Western populations. Indians residing in Westernized countries, particularly second-generation immigrants, exhibit an increased risk of developing inflammatory bowel disease (IBD). The Gibson lab’s previous research had associated western dietary acculturation in Canada with significant changes in the gut microbiome of these populations. Specifically, the consumption of UPFs, a lack of fiber, and alcohol intake had been identified as key factors distinguishing Westernized gut microbiomes from those of Indian origin. Since previous epidemiological research had revealed Indo-Canadians had an increased risk of getting IBD in Canada, we aimed to determine whether changes in the gut microbiome affected susceptibility to ulcerative colitis among Indians in westernized countries. To do this, germ-free (GF) mice were colonized with fecal microbiota transplants (FMTs) from Indo-Canadian (born in Canada from parents of Indian origin) or Indo-Immigrant (born in India and immigrated to Canada as adults) donors. GF C57BL/6 mice were orally gavaged twice and then administered 2% dextran sulfate sodium (DSS) for five days to induce colitis. Disease severity was assessed through clinical scoring, histological evaluation, and quantification of inflammatory biomarkers. Mice colonized with Indo-Canadian fecal transplants exhibited greater susceptibility to DSS-induced colitis, evidenced by elevated inflammatory markers including fecal calprotectin, lipocalin-2 (LCN-2), and TNF-α. They also displayed evidence that there was increased intestinal barrier permeability before colitis evident by the presence of commensal bacteria measured in the submucosal area of the colon. These mice also exhibited higher levels of short-chain fatty acids (SCFAs). These findings suggest that western dietary acculturation alters the gut microbiome in ways that may increase susceptibility to intestinal inflammation, demonstrating a potential link between industrialization, microbiome composition, and IBD risk among immigrant populations.