The gut microbiome is associated with susceptibility to febrile malaria in Malian children

Kristin M. Ham, Layne K. Bower, Shanping Li, Hernan Lorenzi, Safiatou Doumbo, Didier Doumtabe, Kassoum Kayentao, Aissata Ongoiba, Boubacar Traore, Peter D. Crompton and Nathan W. Schmidt ()
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Kristin M. Ham: Indiana University School of Medicine
Layne K. Bower: Indiana University School of Medicine
Shanping Li: National Institutes of Health
Hernan Lorenzi: J. Craig Venter Institute
Safiatou Doumbo: Techniques and Technologies of Bamako
Didier Doumtabe: Techniques and Technologies of Bamako
Kassoum Kayentao: Techniques and Technologies of Bamako
Aissata Ongoiba: Techniques and Technologies of Bamako
Boubacar Traore: Techniques and Technologies of Bamako
Peter D. Crompton: National Institutes of Health
Nathan W. Schmidt: Indiana University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Malaria is a major public health problem, but many of the factors underlying the pathogenesis of this disease are not well understood, including protection from the development of febrile symptoms, which is observed in individuals residing in areas with moderate-to-high transmission by early adolescence. Here, we demonstrate that susceptibility to febrile malaria following Plasmodium falciparum infection is associated with the composition of the gut microbiome prior to the malaria season in 10-year-old Malian children, but not in younger children. Gnotobiotic mice colonized with the fecal samples of malaria-susceptible children were shown to have a significantly higher parasite burden following Plasmodium infection compared to gnotobiotic mice colonized with the fecal samples of malaria-resistant children. The fecal microbiome of the susceptible children was determined to be enriched for bacteria associated with inflammation, mucin degradation and gut permeability, and to have increased levels of nitric oxide-derived DNA adducts and lower levels of mucus phospholipids compared to the resistant children. Overall, these results indicate that the composition of the gut microbiome is associated with the prospective risk of febrile malaria in Malian children and suggest that modulation of the gut microbiome could decrease malaria morbidity in endemic areas.

Date: 2024
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DOI: 10.1038/s41467-024-52953-8

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