Gut dysbiosis in patients with multiple sclerosis

An essential function of gut microbiota is regulating immune responses, including T lymphocyte functions in health and disease. We hypothesized that gut microbiota contribute to the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the nervous system characterized by significant involvement of T lymphocytes. We analyzed the microbiome of stool samples from treatment-naïve MS patients and healthy controls using amplicon sequencing of 16S V4 region. Although we did not observe major global shifts in microbial community structure, we were able to identify individual microbial taxa that were significantly associated with MS and study their functions on regulating primary human T lymphocyte differentiation in vitro. First, we discovered that MS patients exhibited less Treg differentiation in response to their own microbiota. Furthermore, MS-associated bacteria Acinetobacter calcoaceticus was sufficient to reduce Treg differentiation and increase Th1 and Th2 lymphocyte differentiation. The expansion of Th1 lymphocytes was recapitulated by Akkermansia muciniphila, which was similarly more abundant in MS patients. In contrast, Parabacteroides distasonis, which was significantly reduced in MS microbiome, stimulated 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. This study is the first to demonstrate the functional effects of gut dysbiosis in MS on host immunity and forms a basis for future research on microbial functions in regulating the adaptive autoimmune responses.