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

Martin Stražar, Godfrey S. Temba, Hera Vlamakis, Vesla I. Kullaya, Furaha Lyamuya, Blandina T. Mmbaga, Leo A. B. Joosten, Andre J. A. M. Ven, Mihai G. Netea (), Quirijn Mast and Ramnik J. Xavier ()
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Martin Stražar: Broad Institute of MIT and Harvard
Godfrey S. Temba: Kilimanjaro Christian Medical University College
Hera Vlamakis: Broad Institute of MIT and Harvard
Vesla I. Kullaya: Kilimanjaro Christian Medical Centre
Furaha Lyamuya: Kilimanjaro Christian Medical University College
Blandina T. Mmbaga: Kilimanjaro Christian Medical Centre
Leo A. B. Joosten: Radboud University Medical Center
Andre J. A. M. Ven: Radboud University Medical Center
Mihai G. Netea: Radboud University Medical Center
Quirijn Mast: Radboud University Medical Center
Ramnik J. Xavier: Broad Institute of MIT and Harvard

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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. Here, we uncover a gradient of intestinal microbial compositions from rural through urban Tanzanian, towards European samples, manifested both in relative abundance and genomic variation observed in stool metagenomics. The rural population shows increased Bacteroidetes, led by Prevotella copri, but also presence of fungi. Measured ex vivo cytokine responses were significantly associated with 34 immunomodulatory microbes, which have a larger impact on circulating metabolites than non-significant microbes. Pathway effects on cytokines, notably TNF-α and IFN-γ, 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.

Date: 2021
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DOI: 10.1038/s41467-021-25213-2

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