Probiotic T-cell centered immunoregulation

Background: The gut microbiota represents an important contributor to (auto-) immune processes in people with multiple sclerosis (pwMS). A beneficial modulation of the microbiota composition by probiotic intake might represent an interesting therapeutic strategy in the treatment of MS. First clinical studies suggest a beneficial effect on the clinical outcome, but a potential mechanism involving peripheral immune responses and the gut (microbiota) have not been investigated so far. Objectives: To determine the potential immunomodulatory effect of probiotic supplementation in pwMS. Methods: 28 pwMS (46% female, mean age 45 (21-64) years, 77% RRMS, median disease duration 11 ± 9 years, median EDSS 3 ± 2) and 41 HC (63% female, mean age 27 (21-63) years) supplemented a lactobacillus containing probiotic named Vivomixx® for two weeks. PwMS supplemented the probiotic add-on to their immunotherapy. We performed in depth immune cell phenotyping in blood samples before and after probiotic intake, complemented by mRNA expression analysis, serum cytokine measurement and Treg suppression assays. Microbiota metabolites were investigated in stool and serum samples by mass spectrometry and validated in in vitro T cell differentiation assays. Results: Two weeks of probiotic supplementation resulted in a significant increase of regulatory T cells (Treg) in pwMS and HC, whereas T helper (Th) 1 cells were reduced significantly in pwMS. This was paralleled by increased concentrations of interleukin (IL-) 10 in serum and an enhanced expression of Il10 and Ctla4 in isolated peripheral blood mononuclear cells. Functional assays before and after probiotic intake revealed an enhanced suppressive capacity of Treg cells. We detected increased concentrations of the tryptophan metabolite indole-3-acetate (IAc) in stool and serum samples of pwMS after probiotic intake compared to baseline. Treatment of CD4+ T cells with IAc in vitro resulted in an increased formation of IL-10 secreting T cells together with increased Cyp1a1 expression, thus potentially involving aryl hydrocarbon receptor (AHR) signaling. Conclusion: Probiotic lactobacilli can serve as an immunomodulatory compound add-on to existing MS therapies, probably by enhancing the formation of AHR agonists in the gut.