Bidirectional Mendelian randomization links gut microbiota to primary biliary cholangitis

Area of Science:

• Gastroenterology
• Microbiology
• Genetics

Background:

• Primary biliary cholangitis (PBC) and gut microbiota (GM) share epidemiological links, but causal relationships are unclear.
• Understanding these links is crucial for developing novel therapeutic interventions for PBC.

Purpose of the Study:

• To investigate the causal relationships between gut microbiota and primary biliary cholangitis using Mendelian randomization.
• To explore the bidirectional causal effects between specific gut bacteria taxa and PBC.

Main Methods:

• Utilized large-scale GWAS data for gut microbiota (MiBioGen) and PBC.
• Employed bidirectional two-sample Mendelian randomization (MR) with inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO methods.
• Assessed heterogeneity using Cochran's Q statistic and MR-Egger intercept test.

Main Results:

• Genetically determined order Coriobacteriales was associated with increased PBC risk (OR=2.18).
• Genetically determined class Deltaproteobacteria showed a causal effect in decreasing NAFLD risk (OR=0.52).
• PBC progression was linked to increased abundance of Bacteroidia, Bacteroidales, and Bacteroidetes, and decreased abundance of Lachnospiraceae UCG010.

Conclusions:

• Genetically driven gut bacteria, specifically order Coriobacteriales and class Deltaproteobacteria, have a causal role in PBC risk.
• PBC itself influences the abundance of specific gut microbiota taxa, including Bacteroidia, Bacteroidales, Bacteroidetes, and Lachnospiraceae UCG010.
• Modulating gut microbiota presents a potential therapeutic avenue for managing primary biliary cholangitis.