Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation
Microbiome-based therapies are promising new treatment avenues. While global alterations in microbiota composition have been shown in multiple sclerosis, whether and how gut microbiota influence autoimmune responses in an antigen-specific manner is unclear. Here, we genetically engineered gut bacteria to express a brain antigen and dissect their pathogenic potential in a murine model of autoimmune neuroinflammation. Colonization with bacteria expressing myelin - but not ovalbumin-peptide exacerbates an encephalitogenic immune response in the gut by activating antigen-specific T cells as well as B cells leading to accelerated neuroinflammatory disease. These results demonstrate how antigen-specific microbial modulation can influence autoimmunity, providing insight for development of therapeutic strategies targeting specific bacterial taxa for treatment of MS and other autoimmune diseases.
Authors
- Kristina Berve (ORCID: https://orcid.org/0009-0006-1680-7222)
- David Schreiner (ORCID: https://orcid.org/0000-0003-0324-2526)
- Sergio E. Baranzini (ORCID: https://orcid.org/0000-0003-0067-194X)
- A Macpherson
- Julia Dyckow (ORCID: https://orcid.org/0000-0003-1423-9322)
- Sharon A. Sagan (ORCID: https://orcid.org/0009-0008-2212-5783)
- Scott S. Zamvil (ORCID: https://orcid.org/0000-0003-2720-9915)
- Joseph J. Sabatino (ORCID: https://orcid.org/0000-0002-6804-7441)
- Amel Zulji (ORCID: https://orcid.org/0000-0002-5185-1898)
- Stephanie C. Ganal‐Vonarburg (ORCID: https://orcid.org/0000-0002-2548-7754)
- Lena K. Siewert (ORCID: https://orcid.org/0000-0003-3808-3377)
- Aida Muñoz-Blázquez (ORCID: https://orcid.org/0000-0003-1009-8593)
- Lucas Schirmer (ORCID: https://orcid.org/0000-0001-7142-4116)
- Ryan Baumann
- Elisabeth Pössnecker (ORCID: https://orcid.org/0000-0002-6271-2404)
- Kazuki Nagashima (ORCID: https://orcid.org/0000-0002-8593-136X)
- Gurumoorthy Krishnamoorthy
- Charlotte Nelson
- Anne-Katrin Pröbstel
- Médéric Diard
- Michael A. Fischbach
Institutions
- University of Bern (CH)
- University of Mannheim (DE)
- University of Basel (CH)
- Neurosciences Institute (US)
- Heidelberg University (DE)
- University Hospital Bonn (DE)
- University Hospital of Bern (CH)
- German Center for Neurodegenerative Diseases (DE)
- University Hospital Heidelberg (DE)
- University Hospital of Basel (CH)
- University of California System (US)
- Hospital Base (CL)
- Center for Human Genetics (US)
- Chan Zuckerberg Initiative (United States) (US)
- Center for Neurosciences (US)
- Department of Biomedicine Basel (CH)
- European Society of Clinical Microbiology and Infectious Diseases (CH)
- Bioengineering Center (RU)
- Institute of Bioinformatics (IN)
- University Medical Centre Mannheim (DE)
- Stanford University (US)
Publication Details
- Journal
- Gut Microbes
- Published
- 2025-12-24
- DOI
- https://doi.org/10.1080/19490976.2025.2601430
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fondation Pierre Mercier
- Fondation Pierre Mercier pour la Science
- National Institutes of Health
- University of California, San Francisco