A secondary metabolite of Limosilactobacillus reuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosis
Summary: Limosilactobacillus reuteri is an immunomodulatory bacterium enriched in non-industrialized microbiomes, making it a therapeutic candidate for chronic diseases. However, effects of L. reuteri strains in mouse models of multiple sclerosis have been contradictory. Here, we show that treatment...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000920 |
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| author | Dale Archer María Elisa Pérez-Muñoz Stephanie Tollenaar Simona Veniamin Naomi Hotte Christopher C. Cheng Kristoff Nieves Jee-Hwan Oh Lilian Morceli Susan Muncner Daniel R. Barreda Gurumoorthy Krishnamoorthy Christopher Power Jan-Peter van Pijkeren Jens Walter |
| author_facet | Dale Archer María Elisa Pérez-Muñoz Stephanie Tollenaar Simona Veniamin Naomi Hotte Christopher C. Cheng Kristoff Nieves Jee-Hwan Oh Lilian Morceli Susan Muncner Daniel R. Barreda Gurumoorthy Krishnamoorthy Christopher Power Jan-Peter van Pijkeren Jens Walter |
| author_sort | Dale Archer |
| collection | DOAJ |
| description | Summary: Limosilactobacillus reuteri is an immunomodulatory bacterium enriched in non-industrialized microbiomes, making it a therapeutic candidate for chronic diseases. However, effects of L. reuteri strains in mouse models of multiple sclerosis have been contradictory. Here, we show that treatment of spontaneous relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice with L. reuteri R2lc, a strain that activates the aryl hydrocarbon receptor (AhR) through the pks gene cluster, resulted in severe pathology. In contrast, a pks mutant and a pks-negative strain (PB-W1) failed to exacerbate EAE and exhibited reduced pathology compared to R2lc despite earlier disease onset in PB-W1 mice. Differences in pathology occurred in parallel with a pks-dependent downregulation of AhR-related genes, reduced occludin expression in the forebrain, and altered concentrations of immune cells. This work establishes a molecular foundation for strain-specific effects on autoimmunity, which has implications for our understanding of how microbes contribute to chronic conditions and the selection of microbial therapeutics. |
| format | Article |
| id | doaj-art-919455cf314d4dc4a2283051cb7b4dbe |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-919455cf314d4dc4a2283051cb7b4dbe2025-08-20T02:14:50ZengElsevierCell Reports2211-12472025-03-0144311532110.1016/j.celrep.2025.115321A secondary metabolite of Limosilactobacillus reuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosisDale Archer0María Elisa Pérez-Muñoz1Stephanie Tollenaar2Simona Veniamin3Naomi Hotte4Christopher C. Cheng5Kristoff Nieves6Jee-Hwan Oh7Lilian Morceli8Susan Muncner9Daniel R. Barreda10Gurumoorthy Krishnamoorthy11Christopher Power12Jan-Peter van Pijkeren13Jens Walter14Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Medicine, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada; Center of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada; Center of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB T6G 2R3, CanadaAPC Microbiome Ireland, University College Cork, Cork T12 K8AF, County Cork, Ireland; School of Microbiology, University College Cork, Cork T12 K8AF, County Cork, Ireland; Department of Medicine, University College Cork, Cork T12 K8AF, County Cork, IrelandDepartment of Food Science, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Biological Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaMax Planck Institute of Biochemistry, 82152 Martinsried, GermanyDepartment of Medicine, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Food Science, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Biological Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada; APC Microbiome Ireland, University College Cork, Cork T12 K8AF, County Cork, Ireland; School of Microbiology, University College Cork, Cork T12 K8AF, County Cork, Ireland; Department of Medicine, University College Cork, Cork T12 K8AF, County Cork, Ireland; Corresponding authorSummary: Limosilactobacillus reuteri is an immunomodulatory bacterium enriched in non-industrialized microbiomes, making it a therapeutic candidate for chronic diseases. However, effects of L. reuteri strains in mouse models of multiple sclerosis have been contradictory. Here, we show that treatment of spontaneous relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice with L. reuteri R2lc, a strain that activates the aryl hydrocarbon receptor (AhR) through the pks gene cluster, resulted in severe pathology. In contrast, a pks mutant and a pks-negative strain (PB-W1) failed to exacerbate EAE and exhibited reduced pathology compared to R2lc despite earlier disease onset in PB-W1 mice. Differences in pathology occurred in parallel with a pks-dependent downregulation of AhR-related genes, reduced occludin expression in the forebrain, and altered concentrations of immune cells. This work establishes a molecular foundation for strain-specific effects on autoimmunity, which has implications for our understanding of how microbes contribute to chronic conditions and the selection of microbial therapeutics.http://www.sciencedirect.com/science/article/pii/S2211124725000920CP: Microbiology |
| spellingShingle | Dale Archer María Elisa Pérez-Muñoz Stephanie Tollenaar Simona Veniamin Naomi Hotte Christopher C. Cheng Kristoff Nieves Jee-Hwan Oh Lilian Morceli Susan Muncner Daniel R. Barreda Gurumoorthy Krishnamoorthy Christopher Power Jan-Peter van Pijkeren Jens Walter A secondary metabolite of Limosilactobacillus reuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosis Cell Reports CP: Microbiology |
| title | A secondary metabolite of Limosilactobacillus reuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosis |
| title_full | A secondary metabolite of Limosilactobacillus reuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosis |
| title_fullStr | A secondary metabolite of Limosilactobacillus reuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosis |
| title_full_unstemmed | A secondary metabolite of Limosilactobacillus reuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosis |
| title_short | A secondary metabolite of Limosilactobacillus reuteri R2lc drives strain-specific pathology in a spontaneous mouse model of multiple sclerosis |
| title_sort | secondary metabolite of limosilactobacillus reuteri r2lc drives strain specific pathology in a spontaneous mouse model of multiple sclerosis |
| topic | CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000920 |
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