Increased intestinal Lactobacillus abundance in post-pancreatectomy steatotic liver disease is associated with altered bile acid metabolism and FXR–FGF19 pathway suppression

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Steatotic liver disease, a common metabolic disorder characterized by hepatic fat accumulation, is frequently associated with altered bile acid metabolism. Post-pancreatectomy steatotic liver disease (PPSLD) develops in approximately 37% of patients undergoing pancreaticoduodenectomy and can progress to steatohepatitis, liver failure, or death. Here, we investigated microbial, bile acid, and metabolic features associated with PPSLD across two clinical cohorts. Patients with PPSLD exhibited a consistent increase in facultative anaerobes, particularly Lactobacillus species, together with an increased predicted capacity for bile acid deconjugation. This microbial profile was associated with higher circulating levels of deconjugated bile acids and a biochemical pattern suggestive of attenuated intestinal FXR–FGF19 signaling and increased hepatic bile acid synthesis. In addition, patients with PPSLD exhibited lower plasma choline and carnitine levels, indicating reduced availability of nutrients essential for phospholipid and fatty acid metabolism. These findings suggest that microbial dysbiosis, bile acid dysregulation, and postoperative nutrient limitations are associated with the PPSLD phenotype, in addition to pancreatic exocrine insufficiency. This study identifies integrated microbial and metabolic alterations associated with PPSLD. While causal relationships cannot be inferred from these observational data, our results may inform future investigations into therapeutic strategies aimed at maintaining metabolic and microbial homeostasis in post-pancreatectomy patients.

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