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Published February 1, 2017 | public
Journal Article

The MS-Associated Gut Microbiome

Abstract

Category: Microbiome Background: An essential function of the gut microbiota is to regulate immune responses, including T lymphocyte functions in health and disease. Objectives: We hypothesized that gut microbiota contribute to the pathogenesis of MS. Methods: We analyzed the microbiome of stool samples from 64 treatment-naïve MS patients and 68 healthy controls using amplicon sequencing of the 16S V4 region of the rRNA gene. We characterized immune profiles of cultured PBMC in response to specific bacteria harbored by MS patients. Results: We found that MS patients exhibited impaired in-vitro Treg differentiation in response to their own microbiota. No major shifts in microbial community structure were observed. However, we were able to identify individual microbial taxa that were significantly associated with MS and studied their ability to regulate primary human T lymphocyte differentiation in vitro. We next conducted in-vitro assays to characterize the functional properties of the MS gut microbiota. We found that MS-associated Acinetobacter calcoaceticus was sufficient to reduce Treg differentiation and increase both Th1 and Th2 differentiation. The expansion of Th1 lymphocytes was recapitulated by Akkermansia muciniphila, which was also more abundant in MS patients. In contrast, Parabacteroidesdistasonis, which was significantly reduced in MS microbiomes, stimulated CD4+ T lymphocyte differentiation into a CD25+ IL-10+ regulatory phenotype. Our results suggest that MS-associated changes in microbiota alter T lymphocyte differentiation in a complex fashion and likely through multiple mechanisms. Finally, microbiota transplants from MS patients into germ-free mice results in more severe experimental autoimmune encephalomyelitis and reduced Tregs compared to controls. Conclusion: This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a novel treatment for MS.

Additional Information

© 2017 SAGE Publications.

Additional details

Created:
August 19, 2023
Modified:
October 25, 2023