Impact of Gut Microbiota Alterations on Mitochondrial Bioenergetics in Cortical Astrocytes and Sensorimotor Impairment in a Rat Model of LPS-Associated Encephalopathy.
Journal
Shock (Augusta, Ga.)
Journal Volume
65
Journal Issue
2
Pages
316 - 328
ISSN
1540-0514
Date Issued
2026-02-01
Author(s)
Abstract
Purpose: – 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. © 2025
Subjects
Astrocyte
fecal microbiota transplantation
lipopolysaccharide-associated encephalopathy
microbiota-gut-brain axis
mitochondrial bioenergetics
short-chain fatty acid
Type
journal article