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

## TL;DR

After pancreatectomy, increased Lactobacillus in the gut is linked to changes in bile acid metabolism and reduced FXR–FGF19 signaling, contributing to liver disease.

## Contribution

Identifies microbial and metabolic alterations in post-pancreatectomy steatotic liver disease, linking Lactobacillus abundance to bile acid and nutrient changes.

## Key findings

- PPSLD patients show increased Lactobacillus and bile acid deconjugation capacity.
- Altered FXR–FGF19 signaling and reduced choline/carnitine levels are observed in PPSLD.
- Microbial dysbiosis and bile acid dysregulation are associated with PPSLD progression.

## Abstract

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.