Abstract
SummaryLarge-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.
Highlights
Mechanistic studies have provided causal linkages between the human gut microbiome and diseases ranging from inflammatory bowel disease (Britton et al, 2019; Ni et al, 2017) to atherosclerosis (Koeth et al, 2013), obesity (Ridaura et al, 2013), diabetes (Uusitalo et al, 2016; Zhang et al, 2020), and mental disorders (Zheng et al, 2016, 2019)
We identified that most of the US (85.3% ± 7.7%) and GUAT (70.7% ± 20.2%) microbiomes are composed of amplicon sequence variants (ASVs) that were successfully transferred from the corresponding donor (Figures S2B–S2D)
The gut microbiomes of these mice did not change significantly post-infection (Figure 3C; Figure S6). These results indicate that the observed differences in susceptibility to infection may be limited to the mucosal T-helper 17 (Th17) pathway within our experimental setup
Summary
Mechanistic studies have provided causal linkages between the human gut microbiome and diseases ranging from inflammatory bowel disease (Britton et al, 2019; Ni et al, 2017) to atherosclerosis (Koeth et al, 2013), obesity (Ridaura et al, 2013), diabetes (Uusitalo et al, 2016; Zhang et al, 2020), and mental disorders (Zheng et al, 2016, 2019). Species of the Prevotella genus, which dominate many microbiomes in low- and middle-income countries, have been linked to improved glucose metabolism in Swedish adults (Kovatcheva-Datchary et al, 2015) Both the Prevotella and Bacteroides genera have been associated in other clinical and mouse studies with rheumatoid arthritis (Maeda et al, 2016; Scher et al, 2013), hypertension (Scher et al, 2013), obesity (Hu et al, 2015), and inflammatory bowel disease (Hickey et al, 2015; Saitoh et al, 2002) in high-income settings. It is very difficult to translate the roles of specific members of each population’s
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