Javier Ochoa-Repáraz
Boise State University, USA
Title: Neurotransmitter-producing probiotics for the treatment of CNS inflammatory demyelination
Biography
Biography: Javier Ochoa-Repáraz
Abstract
Statement of the Problem: Multiple sclerosis (MS) is a devastating autoimmune disease characterized by inflammatory demyelination of the central nervous system (CNS). Over 2.8 million patients are affected worldwide. The gut-microbiota-brain axis has emerged as a critical pathway in the regulation of neuroinflammation. The gut microbiome regulates the severity of many experimental models of autoimmune central nervous system (CNS) inflammatory demyelination. Our most recent findings demonstrate that the microbiota of mice from different sources affects the severity of CNS inflammatory demyelination in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Neuroinflammation modified the gut microbiota composition. The disease progression resulted in a significant reduction in members of lactic acid bacteria. Among the altered taxa, bacteria producing gamma-aminobutyric acid (GABA) were significantly reduced. We hypothesized that modifying the microbiota with a probiotic while increasing intestinal GABA levels would reduce EAE's severity. Methodology: We genetically engineered a Lactococcus lactis with increased GABA production and used the EAE model induced in C57BL/6 mice from two different commercial vendors to test its protective efficacy. Results: Real-time quantitative PCR data demonstrated an elevated expression of glutamic acid decarboxylase (GAD), while GABA-specific ELISA showed a significant increase in neurotransmitter production when exposed to increasing concentrations of glutamic acid and time. In vivo, five times/week oral gavages with 5 x 108 CFU/mouse of GAD L. lactis but not with empty-plasmid carrier L. lactis protected against EAE compared with sham-treated mice, while preventing weight loss. However, protection was dependent on the initial composition of the microbiome. Conclusion & Significance: Our results show that the increase of GABA at the intestinal level with the oral treatment with a probiotic strain protects against neuroinflammation in the CNS.