Gut microbiota, immune cells, and chronic sinusitis: A Mendelian randomization analysis

Area of Science:

• Microbiome research
• Immunology
• Genetics

Background:

• Allergic rhinitis (AR) is a widespread upper respiratory inflammatory condition.
• The link between gut microbiota and AR is suggested but not causally established.
• Confounding factors and reverse causality obscure the relationship between gut microbiota and AR.

Purpose of the Study:

• To establish a causal relationship between gut microbiota, immune responses, and AR.
• To investigate the mediating role of immune cell proportions in the gut microbiota-AR axis.
• To leverage Mendelian randomization (MR) for robust causal inference.

Main Methods:

• A 2-sample Mendelian randomization (MR) approach was employed.
• Genome-wide association study (GWAS) data from FINRISK 2002 and UK Biobank were utilized.
• Inverse variance weighting (IVW) was applied to assess causal effects and mediation.

Main Results:

• MR analysis identified 17 gut microbiomes associated with chronic rhinosinusitis (CRS) risk.
• Specific microbes like CAG-884 and UBA1407 increased CRS risk; Atopobiaceae and Bacteroides thetaiotaomicron reduced it.
• CAG-884 causally influenced CRS risk via mediating the proportion of TD double negative T cells (36.4% mediation).

Conclusions:

• A causal link exists between gut microbiota composition and CRS risk.
• Immune cell proportions, particularly TD double negative T cells, mediate the effect of gut microbes on CRS.
• Findings highlight the gut microbiome's role in upper respiratory tract inflammation.