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)
- Julia Dyckow (ORCID: https://orcid.org/0000-0003-1423-9322)
- Sharon A. Sagan (ORCID: https://orcid.org/0009-0008-2212-5783)
- 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)
- Scott Zamvil
- Anne-Katrin Pröbstel
- Médéric Diard
- Andrew J. Macpherson
- Sergio E Baranzini
- Gurumoorthy Krishnamoorthy
- Michael A Fischbach
- Charlotte Nelson
Institutions
- Tracer Technologies (United States) (US)
Publication Details
- Journal
- Open Access CRIS of the University of Bern
- Published
- 2025-12-31
- DOI
- https://doi.org/10.48620/93637
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00