Huang Chun-Ta, Wang Ying-Chou, Lin Shih-Chang, Lai Yen-Chi, Chen Seu-Hwa, Feng Shu-Ting, Tsai Yi-Ju
Department of Clinical Psychology, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Division of Allergy and Immunology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan.
Shock. 2025 Jun 23. doi: 10.1097/SHK.0000000000002637.
Brain dysfunction is a significant complication of sepsis, commonly referred to as sepsis-associated encephalopathy (SAE). Alterations in gut microbiota during sepsis may contribute to development of SAE through the gut-brain axis. This study investigated effects of fecal transplantation from healthy or endotoxemic individuals on gut microbiota and brain function in a rat model of lipopolysaccharide (LPS)-associated encephalopathy.
Following LPS induction, rats received daily oral gavage of fecal microbiota transplants for three days. Sensory and motor functions were assessed daily throughout the seven-day study period after LPS exposure. On day seven post-LPS, the study examined gut microbiota structure and composition, serum and fecal short-chain fatty acids (SCFAs) levels, ileal villus length, intestinal permeability, neuronal and glial ultrastructure, cytokine concentrations (pro-inflammatory and anti-inflammatory), and mitochondrial bioenergetics.
Administration of healthy donor feces preserved gut microbial structure and composition, maintained ileal villus length, and improved intestinal permeability following LPS treatment. Additionally, it increased SCFA levels, reduced pro-inflammatory cytokines, enhanced anti-inflammatory cytokine release, and restored sensitivity to mechanical and thermal stimuli, as well as motor function. Rats treated with healthy donor feces also exhibited reduced neuronal necrosis and a decreased density of mitochondria in cortical astrocytes. Notably, mitochondrial metabolism in LPS-treated rats returned to near-normal levels following treatment with healthy donor feces. In contrast, administration of endotoxemic donor feces exacerbated these effects in LPS-treated rats.
Ameliorating gut dysbiosis prevents mitochondrial dysfunction in astrocytes by promoting SCFA production and enhancing anti-inflammatory cytokine release. This process preserves neuronal integrity and mitigates the severity of encephalopathy.
脑功能障碍是脓毒症的一种重要并发症，通常称为脓毒症相关性脑病（SAE）。脓毒症期间肠道微生物群的改变可能通过肠-脑轴促成SAE的发展。本研究调查了来自健康个体或内毒素血症个体的粪便移植对脂多糖（LPS）相关性脑病大鼠模型中肠道微生物群和脑功能的影响。
在LPS诱导后，大鼠连续三天每日接受粪便微生物群移植的口服灌胃。在LPS暴露后的七天研究期间，每天评估感觉和运动功能。在LPS注射后第7天，研究检查了肠道微生物群的结构和组成、血清和粪便短链脂肪酸（SCFA）水平、回肠绒毛长度、肠道通透性、神经元和神经胶质超微结构、细胞因子浓度（促炎和抗炎）以及线粒体生物能量学。
给予健康供体粪便可保留肠道微生物结构和组成，维持回肠绒毛长度，并改善LPS治疗后的肠道通透性。此外，它增加了SCFA水平，降低了促炎细胞因子，增强了抗炎细胞因子的释放，并恢复了对机械和热刺激的敏感性以及运动功能。用健康供体粪便治疗的大鼠还表现出神经元坏死减少和皮质星形胶质细胞中线粒体密度降低。值得注意的是，用健康供体粪便治疗后，LPS处理的大鼠的线粒体代谢恢复到接近正常水平。相比之下，给予内毒素血症供体粪便会加剧LPS处理大鼠的这些影响。
改善肠道生态失调可通过促进SCFA产生并增强抗炎细胞因子释放来预防星形胶质细胞中的线粒体功能障碍。这一过程保留了神经元的完整性并减轻了脑病的严重程度。
