Effects of Clostridium butyricum and Propionate Intervention on Gut Microbial Diversity in Toxoplasma gondii-Infected Mice

Chronic Toxoplasma gondii (T. gondii) infection can lead to gut microbiota dysbiosis and neurodegeneration, yet the underlying mechanisms remain poorly understood. In this study, we observed a reduction of butyrate-producing bacteria in both Alzheimer's disease patients and T. gondii-infected mice. Supplementation with Clostridium butyricum, a beneficial gut bacterium that produces butyrate, restored gut microbiota balance, improved intestinal barrier integrity, reduced inflammation, and alleviated endotoxemia. Notably, C. butyricum administration also suppressed glial cell activation, protected synaptic structures, and improved behavioral deficits such as cognitive impairment and anxiety-like symptoms. Fecal microbiota transplantation from C. butyricum-treated mice into antibiotic-treated or germ-free mice reproduced these therapeutic effects. These findings suggest that C. butyricum mitigates T. gondii-induced neuropsychiatric disorders by regulating glial-mediated synaptic pruning via the gut-brain axis, supporting its potential as a microbiota-based therapeutic approach.

慢性刚地弓形虫（Toxoplasma gondii，以下简称T. gondii）感染可引发肠道菌群失调与神经退行性病变，但其潜在作用机制仍不甚明晰。本研究中，我们观察到阿尔茨海默病患者与T. gondii感染小鼠体内的产丁酸菌丰度均显著降低。补充丁酸梭菌（Clostridium butyricum）——一种可产生丁酸的有益肠道细菌——可恢复肠道菌群平衡、改善肠道屏障完整性、减轻炎症反应并缓解内毒素血症。值得注意的是，施用丁酸梭菌还可抑制神经胶质细胞激活、保护突触结构，并改善认知障碍与焦虑样症状等行为缺陷。将经丁酸梭菌处理的小鼠的粪便菌群移植至抗生素处理或无菌小鼠体内，可重现上述治疗效果。上述研究结果表明，丁酸梭菌可通过肠-脑轴调控神经胶质细胞介导的突触修剪，从而缓解T. gondii诱导的神经精神疾病，这支持其作为基于菌群的治疗策略的应用潜力。