Metabolic Syndrome Gut Microbial Associations Are Independent Of Country Of Origin: Evidence From African-Origin Populations

Introduction: Changes to the overall diversity and relative abundance of the microbiota have been shown to alter not only the functionality of the gut system, in particular with regards to the metabolic rates and levels of pro-inflammatory cytokines, but also the development of disease states such as metabolic syndrome (METS). The purpose of this study was to explore the composition of the gut microbiota diversity, and metabolic outcomes, across three populations: the United States, Ghana and South Africa. Hypothesis: We assessed the hypothesis that differences between the three populations, including variations in diet, would affect the diversity and composition of the microbiome of the participants; these changes would in turn be reflected in the gut-related metabolic outcomes. Methods: Participants(N=560) provided a fecal sample which was analyzed using the analysis of Composition of Microbiome to identify differentially abundant bacterial exact sequence variants (ESVs), and general linearized models (GLM) to test associations between selected ESVs and gut-related metabolic outcomes. Results: Not surprisingly, macronutrient intake was significantly different across the 3 sites (p<0.001), which resulted in differences in the overall microbial diversity (p<0.01) and composition of pro-inflammatory species such as Bacteroides (p<0.01). There were also differences in the relative abundance of ESVs associated with multiple metabolic functional pathways in participants meeting diagnostic criteria for METS. As the number of positive METs criteria increased, there were a significant decline in the proportions of microbiota associated with fatty acid degradation (p = 0.026) and lipid metabolism (p = 0.041). On the other hand, the abundance of organisms participating in the proinflammatory LPS functional pathway were higher in obese participants when compared to age and location matched non-obese participants. Finally, there the difference across countries bacterial diversity was associated with a differential pro-inflammatory LPS abundance (p<0.01). Conclusion: In conclusion, we found that country of origin was significantly associated with bacterial diversity. These differences were associated with alterations in the bacterial functional metabolic and proinflammatory pathways, suggesting a role in cardiovascular health and the development of the METS.