Gut dysbiosis and jejunal injury in olfactory dysfunction: Experimental characterization and genetic epidemiological...

Olfactory dysfunction (OD) is increasingly recognized not only as a sensory impairment but also as a condition associated with neurodegeneration and gut microbiota dysbiosis. However, the relationship and biological mechanisms linking the gut microbiota to olfactory function remain poorly understood.

We established a thiamazole-induced OD mouse model and evaluated olfactory function (buried food test), olfactory epithelial and jejunal histology, and gut microbiota by 16S rRNA sequencing. We further performed a two-sample Mendelian randomization (MR) analysis using GWAS (genome-wide association study) data from MiBioGen (196 microbial taxa, exposures) and FinnGen (smell/taste disturbance, outcome), with IVW (inverse-variance weighted) as the primary method and multiple sensitivity analyses.

OD mice exhibited body weight loss, olfactory epithelial degeneration, jejunal mucosal injury, and gut dysbiosis (reduced β-diversity, decreased Allobaculum, enriched Acetivibrio, elevated Microbial Dysbiosis Index (MDI)). MR identified eight taxa with genetically predicted associations with smell and taste disturbance: Gordonibacter, Gammaproteobacteria, Family XIII AD3011 group, Coprobacter, and Roseburia increased OD risk, whereas Lachnospiraceae UCG004, Clostridiaceae 1, and the Eubacterium hallii group were protective. Sensitivity analyses showed no significant pleiotropy or heterogeneity was detected.

This study provides integrated experimental and genetic evidence supporting an association between gut microbiota alterations and olfactory-related dysfunction. In mice, thiamazole-induced olfactory injury was accompanied by gut dysbiosis and intestinal pathology, while Mendelian randomization suggested that genetically predicted alterations in specific microbial taxa may influence susceptibility to smell and taste disturbance. These findings support a biologically relevant link between olfactory dysfunction and the gut microbiota, but further studies are needed to clarify directionality and mechanism.