Summary: Large-scale studies of human gut microbiomes have revealed broad differences in composition across geographically distinct populations. Yet, studies examining impacts of microbiome composition on various health outcomes typically focus on single populations, posing the question of whether compositional differences between populations translate into differences in susceptibility. Using germ-free mice humanized with microbiome samples from 30 donors representing three countries, we observe robust differences in susceptibility to Citrobacter rodentium, a model for enteropathogenic Escherichia coli infections, according to geographic origin. We do not see similar responses to Listeria monocytogenes infections. We further find that cohousing the most susceptible and most resistant mice confers protection from C. rodentium infection. This work underscores the importance of increasing global participation in microbiome studies related to health outcomes. Diverse cohorts are needed to identify both population-specific responses to specific microbiome interventions and to achieve broader-reaching biological conclusions that generalize across populations.
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