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First page of Investigating the Impact of the Gut Microbiota on Nasal Polyp Development: Insights from Mendelian Randomization

Background: Chronic rhinosinusitis with nasal polyps has a high post-surgery recurrence, suggesting complex pathology. However, research into underlying mechanisms and contributing factors, such as gut microbiota, is lacking. Objective: We investigated the cause-and-effect relationship between nasal polyps and the gut microbiota and determined the influence of metabolic pathways as possible mediators.   Methods: This study utilized genetic data from genome-wide association studies. The datasets included nasal polyp data from FinnGen (6,841 cases and 308,457 control samples), microbial metabolic pathway data from the Dutch Microbiome Project (7,738 samples), and single nucleotide polymorphisms of the gut microbiota from MiBioGen (18,340 samples). First, two-sample Mendelian randomization (MR) analyses were conducted on the gut microbiota, nasal polyps, and metabolic pathways. Next, a two-step MR was employed for mediation analysis to investigate whether metabolic pathways serve as mediators between the gut microbiota and nasal polyps and to estimate the proportion of the effect of metabolism-mediated gut microbiota on nasal polyps. Results: MR analysis revealed that Alcaligenaceae was associated with a higher risk of nasal polyps by inhibiting enopyranuronate degradation, whereas Desulfovibrionales had the opposite effect by promoting l-isoleucine biosynthesis. In addition, Actinomyces reduced the risk of nasal polyps by inhibiting L-glutamate degradation but also increased the risk by inhibiting sulfate reduction. Conclusion: This study identified a causal relationship between the gut microbiota and nasal polyps, with metabolic pathways as mediators. Our study provides new perspectives and possibilities for the study and treatment of chronic rhinosinusitis with nasal polyps.

Journal Section:
Clinical Allergy
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S. Karger AG, Basel
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2025
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