Neuroprotective effect of a multi strain probiotic mixture in SOD1G93A mice Through reducing SOD1 aggregation and targeting the microbe-gut-brain axis

Abstract Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the formation of intracellular protein aggregations and the selective loss of motor neurons. Inflammatory response imbalance was considered to be a risk factor and disease-modifier and involved in the regulation of abnormal protein aggregation in ALS disease. The “microbiota-gut-brain axis” is a bidirectional communication system, which has been shown play some regulatory role in neuroinflammation and abnormal protein aggregation of neurodegenerative disorders. But whether probiotics can exert effects on ALS disease through “microbiota-gut-brain axis” is not clear. In our present study, we first report on superoxide dismutase 1-positive aggregates in intestinal myenteric neurons of SOD1G93A mice. This phenomenon was accompanied by structural disorder of myenteric neurons and enteric glial cells, impaired barrier function and overactivated pro-inflammatory response in intestine. This pathological change is different in colon and ileum, suggesting that it may be related to the difference of microbiota in their lumen. Oral administration of a multi-strain probiotic mixture containing Lactobacillus acidophilus, Bifidobacterium longum and Enterococcus faecalis not only improved the gut barrier function and pro-inflammatory response of spinal cord and intestine but also reduced aberrant SOD1 aggregation in myenteric neurons and spinal cord. This effect is accompanied by the alteration of gut microbiota composition and the increased level of short-chain fatty acids. Together, these findings might imply a potential benefit of microbiota-gut-brain axis axis-based therapy in ALS.