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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 bacter...

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Main Authors: Siewert, Lena Katharina (Author) , Berve, Kristina (Author) , Pössnecker, Elisabeth (Author) , Dyckow, Julia (Author) , Zulji, Amel (Author) , Baumann, Ryan (Author) , Munoz-Blazquez, Aida (Author) , Krishnamoorthy, Gurumoorthy (Author) , Schreiner, David (Author) , Sagan, Sharon (Author) , Nelson, Charlotte (Author) , Sabatino Jr, Joseph J. (Author) , Nagashima, Kazuki (Author) , Diard, Médéric (Author) , J. Macpherson, Andrew (Author) , Ganal-Vonarburg, Stephanie C. (Author) , Fischbach, Michael A. (Author) , Zamvil, Scott S. (Author) , Schirmer, Lucas (Author) , Baranzini, Sergio E. (Author) , Pröbstel, Anne-Katrin (Author)
Format: Article (Journal)
Language:English
Published: 24 Dec 2025
In: Gut microbes
Year: 2025, Volume: 18, Issue: 1, Pages: 1-20
ISSN:1949-0984
DOI:10.1080/19490976.2025.2601430
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1080/19490976.2025.2601430
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Author Notes:Lena K. Siewert, Kristina Berve, Elisabeth Pössnecker, Julia Dyckow, Amel Zulji, Ryan Baumann, Aida Munoz-Blazquez, Gurumoorthy Krishnamoorthy, David Schreiner, Sharon Sagan, Charlotte Nelson, Joseph J. Sabatino Jr, Kazuki Nagashima, Médéric Diard, Andrew J. Macpherson, Stephanie C. Ganal-Vonarburg, Michael A. Fischbach, Scott S. Zamvil, Lucas Schirmer, Sergio E. Baranzini and Anne-Katrin Pröbstel
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Summary: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.
Item Description:Gesehen am 12.03.2026
Physical Description:Online Resource
ISSN:1949-0984
DOI:10.1080/19490976.2025.2601430

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