Gut microbiota, circulating metabolites, and gallstone disease: a Mendelian randomization study

Area of Science:

• Gastroenterology
• Microbiome Research
• Genetic Epidemiology

Background:

• The association between gut microbiota (GM) and gallstone disease (GSD) is recognized, but a causal relationship remains unconfirmed.
• Investigating causality is crucial for understanding GSD pathogenesis and developing targeted interventions.

Purpose of the Study:

• To elucidate the causal interplay between the gut microbiome and gallstone disease.
• To explore the potential mediating roles of circulating metabolites in the GM-GSD relationship.

Main Methods:

• Utilized bidirectional Mendelian randomization (MR) analyses with Genome-Wide Association Study (GWAS) data for GM and metabolites.
• Employed mediational analyses, two-step MR, and multivariate MR to assess mediating effects.

Main Results:

• Established causal relationships between GSD and six bacterial groups.
• Identified inverse associations for Class Bacilli, Order Lactobacillales, and Genus Coprococcus 2 with GSD risk.
• Found positive associations for Genus Clostridiumsensustricto1, Genus Coprococcus 3, and Genus Peptococcus with GSD risk.
• Suggests Omega-3 polyunsaturated fatty acids (PUFA) mediate the effect of Genus Peptococcus on GSD.

Conclusions:

• Reinforces the causal link between gut microbiome composition and gallstone disease risk.
• Highlights the mediating role of Omega-3 PUFA in the relationship between specific gut bacteria and GSD.