Abstract：
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. A longitudinal investigation was conducted to examine the alterations in the structure of the ileum and colon in mutant superoxide dismutase 1 (SOD1G93A) transgenic mice models of ALS 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 intestine of SOD1G93A mice were analyzed, with a focus on exploring potential protective mechanisms. SOD1G93A mice exhibit various structural abnormalities in the intestine. Oral administration of LBE improved the proinflammatory response, reduced aberrant superoxide dismutase 1 (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. 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 short-chain fatty acids and enhanced autophagy flux.
摘要：
肌萎缩侧索硬化(ALS)是一种以运动神经元选择性丧失为特征的破坏性神经退行性疾病。称为“微生物群-肠-脑”轴的双向通信系统在神经退行性疾病中具有调节功能。益生菌通过“微生物群-肠-脑”轴对ALS的影响仍不确定。通过使用免疫荧光和Western印迹进行了纵向研究，以检查ALS的突变超氧化物歧化酶1（SOD1G93A）转基因小鼠模型中回肠和结肠结构的变化。随后，小鼠口服多菌株益生菌混合物（LBE）或载体，从60日龄开始直到疾病的晚期。这些药剂对行为的影响，肠道菌群，微生物代谢物，并分析了SOD1G93A小鼠的脊髓和肠道的病理过程，重点探索潜在的保护机制。SOD1G93A小鼠在肠道中表现出各种结构异常。口服LBE可改善促炎反应，减少异常超氧化物歧化酶1（SOD1）聚集，并保护SOD1G93A小鼠肠和脊髓中的神经元细胞。此外，LBE治疗导致肠道微生物群的变化，短链脂肪酸水平的增加，和自噬通量的增强。SOD1G93A小鼠在肠道中表现出各种结构异常。LBE可以改善促炎反应，减少异常SOD1聚集，并保护SOD1G93A小鼠脊髓和肠道中的神经元细胞。LBE的积极作用可归因于短链脂肪酸的增加和自噬通量的增强。
