Causal relationship between gut microbiota and constipation: a bidirectional Mendelian randomization study

Area of Science:

• Gastroenterology and Microbiology
• Human Genetics
• Computational Biology

Background:

• Constipation affects 15% of the global population, posing a significant health burden.
• Gut microbiota is increasingly implicated in constipation, but causal links are unclear.
• Observational studies are limited by confounding factors and potential reverse causality.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota and constipation.
• To utilize a bidirectional Mendelian Randomization (MR) approach to address confounding and reverse causality.
• To identify specific bacterial taxa causally associated with constipation risk.

Main Methods:

• Employed genome-wide association studies (GWAS) data from MiBioGen and other consortia.
• Selected genetic variants as instrumental variables (IVs) for 196 bacterial traits and constipation.
• Applied multiple MR methods (IVW, MR Egger, MR-PRESSO) for robust causal inference.

Main Results:

• Identified specific bacteria with protective effects against constipation (e.g., Coprococcus1, Coprococcus3, Desulfovibrio, Flavonifractor, Lachnospiraceae UCG004).
• Found other bacteria associated with increased constipation risk (e.g., Ruminococcaceae UCG005, Eubacterium nodatum group, Butyricimonas, Bacteroidetes).
• Demonstrated a bidirectional relationship, with constipation altering the abundance of taxa like Family XIII, Porphyromonadaceae, and Proteobacteria.

Conclusions:

• Gut microbiota and constipation exhibit a complex, bidirectional genetic interaction.
• Specific bacterial taxa play a causal role in the development or prevention of constipation.
• Findings highlight potential therapeutic targets within the gut microbiome for constipation management.