CHUN-TA HUANGWang, Ying-ChouYing-ChouWangLin, Shih-ChangShih-ChangLinLai, Yen-ChiYen-ChiLaiChen, Seu-HwaSeu-HwaChenFeng, Shu-TingShu-TingFengTsai, Yi-JuYi-JuTsai2026-03-242026-03-242026-02-01https://www.scopus.com/pages/publications/105008958696https://scholars.lib.ntu.edu.tw/handle/123456789/736577Purpose: – 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 LPS-associated encephalopathy. Methods: – Following LPS induction, rats received daily oral gavage of fecal microbiota transplants for 3 days. Sensory and motor functions were assessed daily throughout the 7-day study period after LPS exposure. On day 7 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. Results: – 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. Conclusion: – 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. © 2025enAstrocytefecal microbiota transplantationlipopolysaccharide-associated encephalopathymicrobiota-gut-brain axismitochondrial bioenergeticsshort-chain fatty acidjournal article10.1097/SHK.000000000000263740550557