Gut microbiome-mediated metabolism effects on immunity in rural and urban African populations
Open accessAbstract
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.
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The post-weaning diet, typically rich in high-fiber plant foods in sub-Saharan Africa, may play an important role in modulating the microbiota and selecting for specific strains.
“The post-weaning diet, typically rich in high-fiber plant foods in sub-Saharan Africa, may also play an important role in modulating the microbiota and selecting for specific strains [100,101] .”
From Genome-scale insights into the metabolic landscape and evolutionary development of Bifidobacterium bifidum (2026) · cites this paper as [100]
The Results section on environmental and dietary factors reports that diet is associated with gut-microbiome composition in Tanzanian rural and urban samples, including greater consumption of vegetables and maize porridge in rural samples. The Results section on the urbanization gradient also reports strain-level differences between populations. But the paper does not establish that a post-weaning, high-fiber plant diet selects specific strains; it does not connect the observed strain differences to post-weaning diet. (LLM, conf=0.84)
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- Authors
- Stražar, M., Temba, G. S., Vlamakis, H., Kullaya, V. I., Lyamuya, F., Mmbaga, B. T., Joosten, L. A. B., van der Ven, A. J. A. M., Netea, M. G., de Mast, Q., & Xavier, R. J.
- Affiliations
- Broad Institute (US)
- Kilimanjaro Christian Medical Centre (TZ)
- Radboud University Medical Center (NL)
- Corresponding author
- Netea, Mihai G.
- Xavier, Ramnik J.
- ORCID
- Venue
- Nature Communications
- Published
- 2021-08-11
- Volume
- 12
- Issue
- 1
- Pages
- 4845-4845
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8357928
- OpenAlex
- W3189089978
- Cited by
- 91
- References
- 69
- Citations by year
- 2026: 10 · 2025: 29 · 2024: 23 · 2023: 17 · 2022: 9 · 2021: 3
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Update notices
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (P30DK043351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Keywords
- gut microbiota, immunomodulation, urbanization, urban-rural gradient, African populations, Prevotella copri, Bacteroidetes, fungal microbiota, cytokine response, TNF-α, interferon-gamma, histidine metabolism, arginine metabolism, Bifidobacterium longum, Akkermansia muciniphila, microbial metabolites, Tanzanian population
- MeSH terms
- Gastrointestinal Microbiome, Adult, Arginine, Bacteria, Diet, Female, Histidine, Humans, Male, Rural Population, Socioeconomic Factors, Tanzania, Urban Population, Urbanization, Cytokines, Metabolic Networks and Pathways, Metabolome, Immunomodulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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