Gut microbiome-mediated metabolism effects on immunity in rural and urban African populations

The human gut microbiota is increasingly recognized as an important factor in modulating innate and adaptive immunity through release of ligands and metabolites that translocate into circulation. Urbanizing African populations harbor large intestinal diversity due to a range of lifestyles, providing the necessary variation to gauge immunomodulatory factors. Stool metagenomics uncovers a gradient of intestinal microbial compositions from rural through urban Tanzania, towards European samples, manifested both in relative abundance and genomic variation. The rural population shows increase Bacteroidetes, led by Prevotella copri, but also presence of fungi. Measured ex vivo cytokine responses were significantly associated with 34 significant microbes. Pathway effects on cytokines, notably TNF-alpha and IFN-gamma, differential metabolome analysis and enzyme copy number enrichment converge on histidine and arginine metabolism as potential immunomodulatory pathways mediated by Bifidobacterium longum and Akkermansia muciniphila.