Gut bacteria-derived sphingolipids alter innate immune responses to oral cholera vaccine antigens
The degree of protection conferred after receiving an oral cholera vaccine (OCV) varies based on age, prior exposure to Vibrio cholerae, and unknown factors. Recent evidence suggests that the microbiota may mediate some of the unexplained differences in oral vaccine responses. Here, we use metagenomic sequencing of the fecal microbiota at the time of vaccination and relate microbial features to immune responses after OCV using a reference-independent gene-level method. We find that the presence of sphingolipid-producing bacteria is associated with the development of protective immune responses after OCV. We test these associations by stimulating human macrophages with Bacteroides xylanisolvens metabolites and find that sphingolipid-containing extracts increase innate immune responses to OCV antigens. Our findings demonstrate a new analytic method for translating metagenomic sequencing data into strain-specific results associated with a biological outcome, and in validating this tool, we identify that microbe-derived sphingolipids impact immune responses to OCV antigens.
Authors
- M. Hasanul Kaisar (ORCID: https://orcid.org/0009-0001-6531-1817)
- Fahima Chowdhury (ORCID: https://orcid.org/0000-0002-6688-1395)
- Ana A. Weil (ORCID: https://orcid.org/0000-0002-6170-4306)
- Susan M. Markiewicz (ORCID: https://orcid.org/0009-0002-9695-664X)
- Afroza Akter (ORCID: https://orcid.org/0000-0001-8374-8556)
- Taufiqur Rahman Bhuiyan (ORCID: https://orcid.org/0000-0003-3755-4763)
- Frederick J Heller
- Edward Thomas Ryan (ORCID: https://orcid.org/0009-0005-0169-394X)
- Regina C. LaRocque (ORCID: https://orcid.org/0000-0003-4558-0339)
- Libin Xu (ORCID: https://orcid.org/0000-0003-1021-5200)
- Hasan Al Banna (ORCID: https://orcid.org/0000-0001-7475-6706)
- Polash Chandra Karmakar (ORCID: https://orcid.org/0000-0003-1413-9911)
- Denise Chac (ORCID: https://orcid.org/0000-0002-4183-3899)
- Samuel S. Minot (ORCID: https://orcid.org/0000-0003-1639-3905)
- Jason B. Harris (ORCID: https://orcid.org/0000-0003-3642-5126)
- Emily L. Pruitt (ORCID: https://orcid.org/0000-0001-9522-4311)
- Mia G. Dumayas (ORCID: https://orcid.org/0009-0004-3007-2512)
- Ashraful Islam Khan (ORCID: https://orcid.org/0000-0003-2169-4163)
- Firdausi Qadri (ORCID: https://orcid.org/0000-0002-8928-9888)
- Amelia Rice
- Pinki Dash (ORCID: https://orcid.org/0009-0009-2367-7368)
Institutions
- University of Maryland, Baltimore (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Harvard University (US)
- Duke University (US)
- University of Washington (US)
- International Centre for Diarrhoeal Disease Research (BD)
- Massachusetts General Hospital (US)
- Fred Hutch Cancer Center (US)
- MaineGeneral Medical Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1038/s41467-025-67388-y
- Primary Topic
- Vibrio bacteria research studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Washington
- Global Affairs Canada
- International Centre for Diarrhoeal Disease Research, Bangladesh
- National Institutes of Health
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- Fogarty International Center