Lactobacillus reuteri reduces the severity of experimental autoimmune encephalomyelitis in mice by modulating gut microbiota

Abstract

Abstract The gut microbiome plays an important role in immune function and has been implicated in multiple sclerosis (MS). However, how to modulate microbiota to prevent or treat MS remain largely unknown. Probiotic Lactobacillus reuteri DSM 17938 (L. reuteri) has anti-inflammatory effects in mouse models of neonatal necrotizing enterocolitis and Treg-deficiency-induced autoimmune disease. L. reuteri in these models modulated gut microbiota and microbiota-associated metabolites to inhibit TH1 and TH2 differentiation and their-associated cytokines, significantly ameliorating the severity of these diseases. An in vitro study indicated that L. reuteri inhibits the differentiation of naïve CD4+T cells into TH17 and TH1 cells. We determined the effect of L. reuteri on experimental autoimmune encephalomyelitis (EAE) mouse model, a widely used animal model of MS, a model which is primarily mediated by TH17 and TH1 cells. We discovered that L. reuteri treatment reduced TH1/TH17 cells and their associated cytokines IFN-γ/IL-17 in EAE, inhibiting the development of EAE. We also showed that the loss of diversity in gut microbiota induced by EAE was largely restored by L. reuteri treatment. Taxonomy-based analysis of gut microbiota showed that the “beneficial” genera Bifidobacterium, Prevotella, and Lactobacillus were negatively correlated with EAE clinical severity scores, whereas the genera Anaeroplasma, Rikenellaceae, and Clostridium were positively correlated. Notably, L. reuteri treatment altered the relative abundances of these EAE-associated taxa in mice. In conclusion, probiotic L. reuteri changed gut microbiota to modulate immune responses in EAE, making it a novel candidate in future studies to modify the severity of MS.