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Genetic causal inference reveals chronic rhinosinusitis as a driver of gut microbiome imbalance, strengthening emerging evidence for a bidirectional gut–airway axis.
According to the findings of a new study, chronic rhinosinusitis (CRS) causally shifts gut microbiome composition by reducing Haemophilus parainfluenzae, increasing Bilophila species, and altering key microbial metabolic pathways, with no reverse causal effect from gut dysbiosis.
CRS is now recognized as a systemic inflammatory condition capable of influencing physiological processes far beyond the sinonasal tract. Mounting research points toward a connection between CRS-related inflammation and gut microbial imbalance, but the causal pathway has remained elusive. To address this gap, the study leveraged Mendelian randomization (MR) to investigate whether CRS exerts a direct causal effect on gut microbiome structure and its downstream metabolic functions.
Researchers applied a two-sample, bidirectional MR approach via large genome-wide association study (GWAS) datasets. CRS genetic instruments were identified from the FinnGen cohort, while microbiome composition and metabolic pathway data were obtained from the Dutch Microbiome Project. Genetic information from 334,182 individuals formed the analytical base. Causal effects were estimated via multiple MR methods—including inverse variance weighting, MR-Egger, weighted median, and weighted mode—with sensitivity tests addressing pleiotropy, heterogeneity, and robustness.
Reverse MR analyses further evaluated whether gut microbiome traits might causally influence CRS. In the forward MR analysis, CRS significantly reduced the abundance of Haemophilus parainfluenzae while increasing Bilophila species in the gut. Additionally, CRS was causally linked with key gut microbiota–related metabolic pathways, suggesting broader functional consequences beyond microbial composition (Table 1).
In contrast, reverse MR analysis found no evidence that gut microbiome species or metabolic pathways causally increase CRS risk after correction for multiple testing (p > 0.05/412). The study confirmed a causal role of CRS in reshaping gut microbiome dynamics, reinforcing the biological relevance of gut–airway interactions. This elevated susceptibility to microbial disruption in CRS patients underscores the need for proactive clinical oversight and more detailed mechanistic studies.
Brazilian Journal of Otorhinolaryngology
Alterations of gut microbiome in chronic rhinosinusitis: insights from a mendelian randomization study
Ke-Shuang Wang et al.
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