Gut Microbiome Dysbiosis Promotes Gallstone Formation via Bile Acid Metabolic Disorder: A Multiomics Study.

Gallstone patients showed increased levels of bile salt hydrolase (BSH)-producing bacteria compared to healthy controls.

• A total of 62 gallstone patients and 62 healthy controls were enrolled in this study.
• BSH-producing bacteria that were elevated included genera Bacteroides, Enterococcus, and Bifidobacterium, as well as the family Lactobacillaceae.
• Participants were recruited from health check-up populations, outpatients, and inpatients.
• Fecal samples were analyzed using metagenomic sequencing.

KEGG pathway analysis revealed that significantly enriched signaling pathways in gallstone patients were mainly related to bile acid biosynthesis and lipid and bile acid precursor metabolism.

• Metagenomic sequencing data were subjected to KEGG analysis.
• Enriched pathways were related to bile acid biosynthesis, lipid metabolism, and bile acid precursor metabolism.
• These findings link gut microbial functional capacity to bile acid dysregulation in gallstone disease.

Gallstone patients had increased levels of hydrophobic bile acids and decreased levels of hydrophilic bile acids compared to controls.

• Serum samples were used for bile acid metabolism detection.
• Lithocholic acid (LCA), a hydrophobic bile acid, was elevated in gallstone patients.
• Taurolithocholic acid (TLCA), a hydrophilic bile acid, was decreased in gallstone patients.
• These changes in bile acid composition were identified as a key factor in gallbladder stone formation.

Specific bacterial species showed significant correlations with differential bile acid levels in gallstone patients.

• Bacteroides intestinalis was positively correlated with LCA (a hydrophobic bile acid).
• Bacteroides fragilis was negatively correlated with TLCA (a hydrophilic bile acid).
• These correlations were identified through correlation analysis between differential bile acids and differential bacterial species.
• The authors state these results 'further confirm the role of BSH-active bacteria in bile acid dysregulation.'

The study proposes an 'intestinal microbiota imbalance-bile acid metabolic disorder-gallbladder stone formation' axis as the mechanistic framework for gallstone disease.

• The axis links gut dysbiosis to bile acid dysregulation and ultimately to gallstone formation.
• Accumulation of hydrophobic bile acids is identified as the key mechanistic step in gallbladder stone formation.
• The multiomics approach combined metagenomic sequencing with serum bile acid metabolomics to support this mechanistic model.
• The study suggests this axis could inform microbiota-targeted prevention and treatment strategies.