Lactobacillus reuteri Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Mice by Modulating Gut Microbiota

Abstract

The gut microbiome plays an important role in immune function and has been implicated in multiple sclerosis (MS). However, how and if the modulation of microbiota can prevent or treat MS remain largely unknown. In this study, we showed that probiotic <i>Lactobacillus reuteri</i> DSM 17938 (<i>L. reuteri</i>) ameliorated the development of murine experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, a model which is primarily mediated by T_H17 and T_H1 cells. We discovered that <i>L. reuteri</i> treatment reduced T_H1/T_H17 cells and their associated cytokines IFN-γ/IL-17 in EAE mice. We also showed that the loss of diversity of gut microbiota induced by EAE was largely restored by <i>L. reuteri</i> treatment. Taxonomy-based analysis of gut microbiota showed that three "beneficial" genera <i>Bifidobacterium, Prevotella</i>, and <i>Lactobacillus</i> were negatively correlated with EAE clinical severity, whereas the genera <i>Anaeroplasma, Rikenellaceae</i>, and <i>Clostridium</i> were positively correlated with disease severity. Notably, <i>L. reuteri</i> treatment coordinately altered the relative abundance of these EAE-associated taxa. In conclusion, probiotic <i>L. reuteri</i> changed gut microbiota to modulate immune responses in EAE, making it a novel candidate in future studies to modify the severity of MS.