Gut bacterial dysbiosis in pediatric severe malaria associates with post-discharge mortality
Gut microbiota have been implicated in severe malaria in murine models, but their contribution to the pathogenesis of severe malaria in children is unknown. Here we show through analysis of gut bacteria in stool samples from two separate African studies enrolling children with severe malaria, and children from local communities, that children with severe malaria have gut bacteria dysbiosis. Among children with severe malaria, there is increased abundance of Enterobacteriaceae that associates with multiple clinical complications of severe malaria. Moreover, increased abundance of Escherichia coli was a predictor of post-discharge mortality. Metagenome analysis identify elevated metabolic pathways and genes supporting the utilization of host-derived molecules in children with severe malaria that have the potential to promote the survival and growth of Enterobacteriaceae. Treatments that target Enterobacteriaceae may have the potential to reduce post-discharge mortality in children with severe malaria.
Authors
- Samuel M. Lehman
- Andrea L. Conroy (ORCID: https://orcid.org/0000-0002-5328-6511)
- David Mzinza (ORCID: https://orcid.org/0000-0002-5999-8616)
- Terrie E. Taylor (ORCID: https://orcid.org/0000-0001-7416-3986)
- Olivia J. Bednarski (ORCID: https://orcid.org/0000-0003-3029-8461)
- Chandy C. John (ORCID: https://orcid.org/0000-0002-1634-1411)
- Ruth Namazzi (ORCID: https://orcid.org/0000-0003-2459-6526)
- Karl B. Seydel (ORCID: https://orcid.org/0000-0001-9859-9549)
- Nathan W. Schmidt (ORCID: https://orcid.org/0000-0001-7325-4536)
- Robert Opika Opoka (ORCID: https://orcid.org/0000-0003-3240-2058)
- Tuan M. Tran (ORCID: https://orcid.org/0000-0002-1928-861X)
- Caroline Kazinga
- Jie Ren (ORCID: https://orcid.org/0000-0002-7823-6262)
Institutions
- Malawi University of Science and Technology (MW)
- World Health Organization - Uganda (UG)
- Indiana University School of Medicine
- Kamuzu University of Health Sciences (MW)
- Indiana University – Purdue University Indianapolis (US)
- Makerere University (UG)
- Michigan State University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-31
- DOI
- https://doi.org/10.1038/s41467-025-64632-3
- Citations
- 2
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 3.76
Funders
- Eli Lilly and Company
- Lilly Endowment
- Indiana University Health
- Riley Children's Foundation
- National Institutes of Health
- School of Medicine, Indiana University