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South Asian (SA) Canadian immigrants have a higher risk of developing certain immune-mediated inflammatory diseases compared to non-migrant SAs. We sought to investigate the effect of migration on the gut metagenome and to identify microbiological associations between migration and conditions that may influence the development of immune-mediated inflammatory diseases. Metagenomic analysis of 58 first-generation (GEN1) SA immigrants and 38 unrelated Canadian born children-of-immigrants (GEN2) determined that the time lived in Canada was associated with continued changes in gut microbial communities. Migration of GEN1 to Canada early in life results in a gut community with similarities to GEN2 SA Canadians and non-SA North Americans. Conversely, GEN1 immigrants who arrived recently to Canada exhibited pronounced differences from GEN2, while displaying microbial similarities to a non-migrating SA cohort. Multivariate analysis identified that community composition was primarily influenced by high abundance taxa. Prevotella copri dominated in GEN1 and non-migrant SAs. Clostridia and functionally related Bacteroidia spp. replaced P. copri dominance over generations in Canada. Mutually exclusive Dialister species occurred at differing relative abundances over time and generations in Canada. This shift in species composition is accompanied by a change in genes associated with carbohydrate utilization and short-chain fatty acid production. Total energy derived from carbohydrates compared to protein consumption was significantly higher for GEN1 recent immigrants, which may influence the functional requirements of the gut community. This study demonstrates the associations between migration and the gut microbiome, which may be further associated with the altered risk of immune-mediated inflammatory diseases observed for SA Canadians.

Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to glycolipid antigens found in microbes in a CD1d-dependent manner. iNKT cells exert innate-like functions and produce copious amounts of cytokines, chemokines and cytotoxic molecules within only minutes of activation. As such, iNKT cells can fuel or dampen inflammation in a context-dependent manner. In addition, iNKT cells provide potent immunity against bacteria, viruses, parasites and fungi. Although microbiota-iNKT cell interactions are not well-characterized, mounting evidence suggests that microbiota colonization early in life impacts iNKT cell homeostasis and functions in disease. In this study, we showed that CD1d−/− and Vα14 Tg mice, which lack and have increased numbers of iNKT cells, respectively, had no significant alterations in gut microbiota composition compared to their littermate controls. Furthermore, specific iNKT cell activation by glycolipid antigens only resulted in a transient and minimal shift in microbiota composition when compared to the natural drift found in our colony. Our findings demonstrate that iNKT cells have little to no influence in regulating commensal bacteria at steady state.Abbreviations: iNKT: invariant Natural Killer T cell; αGC: α-galactosylceramide