Analyzing the causal relationship between gut microbiota, metabolites, and constipation: A Mendelian randomization...

Area of Science:

• Gastroenterology and Microbiology
• Investigating the complex interplay between the gut microbiome and human health.
• Focusing on the gut microbiota's role in gastrointestinal disorders.

Background:

• Constipation is a common condition with multifactorial causes.
• Emerging evidence suggests the gut microbiota (GM) and its metabolites are implicated in constipation.
• The precise causal relationship between GM, metabolites, and constipation requires further elucidation.

Purpose of the Study:

• To investigate the causal associations between gut microbiota composition, metabolites, and the development of constipation.
• To utilize Mendelian randomization (MR) to establish causality between GM, metabolites, and constipation.
• To identify specific bacterial taxa and metabolites that causally influence constipation.

Main Methods:

• Employed Mendelian randomization (MR) analyses using large-scale genome-wide association study (GWAS) data.
• Derived genetic instruments from GWAS of European populations for GM (n=18,340), metabolites (n=7824), and constipation (n=47,696).
• Performed sensitivity and reverse MR analyses to ensure robustness and rule out reverse causality.

Main Results:

• Identified positive causal correlations between constipation and Rikenellaceae, Enterorhabdus, FamilyXIIIUCG001, and Victivallison.
• Found negative causal correlations between constipation and Betaproteobacteria, Methanobacteria, Methanobacteriaceae, Coprococcus2, Desulfovibrio, Eubacteriumbrachy group, Haemophilus, Methanobacteriales, and Firmicutes.
• Discovered 24 significant causal relationships between 13 GMs and metabolites, with Methanobacteria, Methanobacteriaceae, and Methanobacteriales positively correlating with specific metabolites.

Conclusions:

• Established a causal relationship between specific gut microbiota, their metabolites, and the development of constipation.
• Highlighted the critical roles of identified bacteria and metabolites in gut barrier integrity, neuronal signaling, and energy metabolism.
• Provides a foundation for developing novel diagnostic and therapeutic strategies for constipation based on gut microbiota modulation.