@Article{biocell.2026.084065,
AUTHOR = {Carlo Acierno, Flavia Carriero, Alfredo Caturano, Ferdinando Carlo Sasso, Salvatore D’Angelo, Luca Rinaldi, Giuseppe Terrazzano},
TITLE = {Microbial-Derived Metabolites as Modulators of Hepatic and Systemic Oxidative Stress: Mechanistic Insights and Clinical Implications},
JOURNAL = {BIOCELL},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/biocell/online/detail/27519},
ISSN = {1667-5746},
ABSTRACT = {Microbiota-derived metabolites have emerged as modulators of hepatic redox biology, because the liver is the first organ to receive and biotransform gut-derived signals through the portal circulation. Oxidative stress is best viewed as a dynamic, compartmentalized redox network rather than a static excess of reactive species. This review provides a liver-centered, mechanistic synthesis of how microbiota-derived products influence hepatic redox balance through receptor sensing, first-pass biotransformation, immunometabolic remodeling, and subcellular stress responses. Particular attention is given to direct microbial metabolites (short-chain fatty acids, indoles, and aromatic derivatives), the trimethylamine/trimethylamine N-oxide axis, bile acid pool remodeling, and lipopolysaccharide. These signals converge on a restricted set of master regulators, namely nuclear factor erythroid 2–related factor 2 (Nrf2), nuclear factor-κB (NF-κB), farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), aryl hydrocarbon receptor (AhR), AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR), thereby modulating mitochondrial, endoplasmic reticulum, peroxisomal, and lysosomal function across the major hepatic cell types. Across major liver diseases, microbiota-derived metabolites may support redox resilience under homeostatic conditions or promote oxidative injury when barrier dysfunction, metabolic vulnerability, or inflammatory priming are present, supporting a shift from a taxonomy-based to a metabolite-centered, function-oriented view of the gut–liver axis.},
DOI = {10.32604/biocell.2026.084065}
}