Causal associations between gut microbiota, metabolites and asthma: a two-sample Mendelian randomization study

Area of Science:

• Microbiome research
• Genetic epidemiology
• Respiratory medicine

Background:

• Observational studies suggest a link between gut microbiota and asthma but are limited by bias and confounding factors.
• The causal relationship between gut microbiota composition and asthma remains unclear.

Purpose of the Study:

• To investigate the potential causal relationships between gut microbiota and asthma using bi-directional Mendelian randomization (MR).
• To assess the causal effect of gut metabolites on asthma.
• To identify specific gut microbes that causally influence asthma risk.

Main Methods:

• Two-sample bi-directional Mendelian randomization (MR) analysis.
• Utilized genetic variants for gut microbiota from MiBioGen, metabolites from TwinsUK and KORA, and asthma data from FinnGen.
• Employed various MR methods and sensitivity analyses for validation.

Main Results:

• Identified nine gut microbes potentially impacting asthma risk.
• Found significant causal relationships for the class Bacilli (OR=0.84) and order Lactobacillales (OR=0.83) after FDR correction.
• Reverse MR analysis showed a potential causal effect of asthma on gut microbes, but this was not significant after correction. No causal effect of gut metabolites on asthma was observed.

Conclusions:

• Provides evidence for a causal role of specific gut microbes, including Bacilli and Lactobacillales, in asthma development.
• Offers insights into microbiota-mediated asthma mechanisms.
• Suggests potential therapeutic targets for asthma prevention and treatment by modulating specific gut microbiota.