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

Introduction: 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. This study aimed to investigate the causal relationship between nasal polyps and gut microbiota, and to identify and quantify the potential mediating roles of metabolic pathways. 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 genus Actinomyces and genus Bifidobacterium are associated with an increased risk of nasal polyps through the inhibition of SO4ASSIM-PWY: sulfate reduction I (assimilatory) and PWY-4242: pantothenate and coenzyme A biosynthesis III, respectively. In contrast, family Desulfovibrionaceae is linked to a reduced risk of nasal polyps by promoting GALACTUROCAT-PWY: d-galacturonate degradation I. Additionally, the order Desulfovibrionales further mitigates the risk of nasal polyps not only by promoting the same GALACTUROCAT-PWY pathway but also by enhancing the ILEUSYN-PWY pathway, which involves l-isoleucine biosynthesis I derived from threonine.

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.