Abstract
OBJECTIVE: Gut microbiome dysbiosis is associated with various diseases. Causal association between Chronic Rhinosinusitis (CRS) and gut microbiome is yet unknown. This study aimed to investigate the potential causal relationship between CRS and gut microbiome dysbiosis. METHODS: We used Genome-Wide Association Study (GWAS) data from FinnGen database for CRS. The Dutch Microbiome Project study provided data on gut microbiota species. A total of 334,182 individuals were included. Two-sample bidirectional Mendelian Randomization (MR) analysis was used to investigate causal relationship between CRS and gut microbiome. The main methods of evaluation were Inverse Variance Weighting (IVW), weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. RESULTS: Forward MR analysis indicated CRS is potentially linked to decreased risk of Haemophilus parainfluenzae (OR = 0.79, 95% CI 0.66‒0.94, p = 0.009) and increased risk of Bilophila's (OR = 1.14, 95% CI 1.02-1.27, p = 0.023) within the gut. Reduced risks in gut microbiota-related pathways like UDP-N-acetyl-d-glucosamine biosynthesis I (OR = 0.85, 95% CI 0.77‒0.94, p = 0.002) and increased risk in pathway NAD biosynthesis I from aspartate (OR = 1.14, 95% CI 1.03-1.27, p = 0.010) were also linked to CRS. Reverse MR analyses, we obtained no positive results (p > 0.05/412). CONCLUSION: This study reveals CRS exerts a causal impact on shifts within the composition of the gut microbiome and also links to the changes of gut microbiota-related metabolic pathways. The risk of changes in gut microbiota should be of greater concern in patients with CRS than in the general population. LEVEL OF EVIDENCE: Mendelian Randomized (MR) studies are second only to randomized controlled trials in terms of the level of evidence.