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Microbial metabolite-mediated gut–liver axis remodeling after hepatectomy: mechanisms and therapeutic opportunities

Year: 2026
Type: review
Abstract: Hepatectomy remains a cornerstone treatment for primary and metastatic liver malignancies, but successful recovery depends on coordinated liver regeneration, immune regulation, metabolic adaptation, and maintenance of intestinal homeostasis. Emerging evidence indicates that the gut-liver axis functions as a critical communication network mediated not only by microbial composition but also by microbial-derived metabolites. Surgical stress, perioperative fasting, antibiotic exposure, ischemia-reperfusion injury, altered portal circulation, and changes in bile acid metabolism can profoundly disrupt intestinal microbial ecology and reshape metabolite production after hepatectomy. This review will summarize current knowledge regarding microbial metabolites, including short-chain fatty acids, bile acid derivatives, indole metabolites, and other bioactive molecules, as regulators of liver regeneration and postoperative recovery. Particular attention will be given to their effects on intestinal barrier integrity, Kupffer cell activation, inflammatory signaling, mitochondrial metabolism, and extracellular matrix remodeling. We will further discuss emerging therapeutic strategies targeting the gut-liver metabolic axis, including nutritional modulation, probiotics, prebiotics, synbiotics, metabolite-based interventions, and microbiota-directed therapies. This review aims to provide a translational perspective on how microbial metabolites may serve as biomarkers and therapeutic targets for optimizing recovery after hepatectomy and improving metabolic resilience in patients undergoing liver surgery.
DOI: 10.3389/fsurg.2026.1951535
Language: English
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222953767
FWCI:
Cites: 76
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Related to: 10