Oral Administration of Probiotic Enterococcus durans to Ameliorate Experimental Autoimmune Encephalomyelitis in Mice

INTRODUCTION: Probiotics, including lactobacilli, have immunomodulatory activities with promising effects on inflammatory diseases. In this study, we evaluate the effect of Enterococcus durans (Edu) and three various strains of lactobacilli (Lacto-mix), including L. rhamnosus, L. casei, and L. plantarum, to prevent Experimental Autoimmune Encephalomyelitis (EAE) features METHODS: C57BL/6 female mice were inoculated with Myelin Oigodendrocyte Glycoprotein (MOG(35-55)) in CFA (complete Freund’s adjuvant) to induce EAE. Five groups (n=6 in each group) of animals received saline or probiotics by oral gavage with 200 μL of lactobacilli (1.5×10(8) CFU/mL) for 2 weeks before the immunization and during the test for one month. RESULTS: Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but a decrease in inflammatory cells in the probiotic-treated animals. Pro-inflammatory cytokines (Interleukin [IL]-17 and Interferon [IFN]-γ) concentration in the supernatant of the brain and spinal cord tissues showed a significant increase in the EAE compared with the normal saline group (P<0.01). While in the spinal cord tissue, there was a decrease in IL-17 in those animals treated with the Lactomix and Edu + Lacto-mix (P<0.01) and a significant decrease in IFN-γ in those animals that received Edu (P<0.05). Western blot analysis of matrix metalloproteinase-9 and myelin basic protein showed a decrease and increase in treatment and EAE groups, respectively, compared to the normal control group. CONCLUSION: Our data suggest that probiotic Enterococcus durans and Lacto-mix prevents EAE, but further studies are needed to clarify the exact mechanisms and their application in preclinical and clinical trials. HIGHLIGHTS: Dysfunction of the blood-brain barrier, migration of inflammatory cells into the Central Nervous System (CNS), and an increase in the pro-inflammatory factors, are the hallmarks in the pathogenesis of Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE). The optimal effects of probiotic strains may involve the simultaneous use of more than one strain. Probiotic Enterococcus durans and Lacto-mix have a preventive effect against EAE. PLAIN LANGUAGE SUMMARY: Multiple Sclerosis (MS) is a myelin-degenerating autoimmune disease in the central nervous system. Experimental Autoimmune Encephalomyelitis (EAE), due to its similar clinical and pathologic features to MS, is widely used in many model studies of this disease. The microbiome refers to a genomic set of germs (bacteria, arches, fungi, and viruses), a commensal flora that lives in the intestine and niche of humans and other mammals. The microbiome affects the host’s physiological system, especially the balance between health and disease. Additionally, the importance of the microbiome is evident in regulating the intestine-brain axis, or the coordination of the digestive and the central nervous system. In this regard, probiotics, including lactobacilli, have antioxidant and anti-inflammatory properties in vitro and in vivo. Probiotic strains have a wide range of health-improvement effects, and a combination of strains with specific properties provides a broader range of antimicrobial spectrum and stronger anti-inflammatory effects. Considering the critical role of probiotics in the immune system, this study aimed to investigate the possible role of Enterococcus durans alone or in combination with Lactobacillus mixture (L. rhamnosus, L. casei, and L. plantarum) on the EAE animal model of MS.