Molecular Patterns Expressed by a Human Gut Commensal Strain of Lactobacillus Suppress Neuroinflammation

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that affects 2.5 million people worldwide. Growing evidence suggests that perturbation of the gut microbiota, a dense collection of microorganisms that colonize the gut, plays a functional role in MS. Utilizing experimental autoimmune encephalomyelitis (EAE), the most commonly used murine model of MS, we previously identified a significant negative correlation between the relative abundance of gut Lactobacillus and the severity of EAE, mirroring what is seen in MS patients. We now report that a human gut-derived commensal strain of Lactobacillus paracasei (Lb) can suppress preclinical murine models of MS with both prophylactic and therapeutic administration. Surprisingly, we found that heat-killed Lb was as effective as live Lb in protecting animals against EAE, as measured by disease score and demyelination. Heat-killed Lb-treated animals had reduced numbers of CNS-infiltrating leukocytes and this was associated with a decrease in select chemokines in the serum. The beneficial effect of heat-killed Lb was dependent on host expression of Toll-like receptor 2 (TLR2), which senses major components of the Lb cell wall, as EAE is not suppressed by heat-killed Lb in TLR2-deficient mice. Thus, Lb-associated molecular patterns may be an important signal to prevent aberrant peripheral immune cell infiltration into the CNS and warrant further investigation as a novel therapy for MS patients.