Neuroprotective effect of a multistrain probiotic mixture in SOD1G93A mice by reducing SOD1 aggregation and targeting the microbiota-gut-brain axis

Abstract Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. A bidirectional communication system known as the “microbiota-gut-brain” axis has a regulatory function in neurodegenerative disorders. The impact of probiotics on ALS through the “microbiota-gut-brain” axis remains uncertain. Methods: A longitudinal investigation was conducted to examine the alterations in the structure of the ileum and colon in SOD1G93A mice by using immunofluorescence and Western blotting. Subsequently, the mice were administered a multistrain probiotic mixture (LBE) or vehicle orally, starting from 60 days of age until the terminal stage of the disease. The effects of these agents on the behavior, gut microbiota, microbial metabolites, and pathological processes of the spinal and intestinal of SOD1G93A mice were analyzed, with a focus on exploring potential protective mechanisms. Results: SOD1G93A mice exhibit various structural abnormalities in the intestine. Oral administration of LBE improved the proinflammatory response, reduced aberrant SOD1 aggregation, and protected neuronal cells in the intestine and spinal cord of SOD1G93A mice. Furthermore, LBE treatment resulted in a change in intestinal microbiota, an increase in short-chain fatty acid levels, and an enhancement in autophagy flux. Conclusions: SOD1G93A mice exhibited various structural abnormalities in the intestine. LBE can improve the proinflammatory response, reduce aberrant SOD1 aggregation, and protect neuronal cells in the spinal cord and intestine of SOD1G93A mice. The positive effect of LBE can be attributed to increased SCFAs and enhanced autophagy flux.