Vaginal resistome redundancy is associated with microbial metabolic potential and host glycomic features in endometriosis

Abstract The vaginal microbiome plays a critical role in reproductive health, yet most studies remain descriptive and functional features connecting microbial communities to host physiology remain poorly understood. In endometriosis, alterations in the vaginal microbiome and host glycosylation have been reported, yet ecological properties connecting these systems remain unclear. We investigated whether vaginal resistome functional redundancy (FR) represents a functional link between microbial community structure, microbial metabolic capacity, and host glycomic variation across endometriosis severity. Shotgun metagenomic sequencing was performed on high vaginal swabs from women with healthy controls, minimal/mild, and moderate/severe endometriosis (n = 40). While total antibiotic resistance genes (ARG) abundance remained relatively stable across disease groups, resistome FR increased significantly in moderate/severe endometriosis, reflecting a transition from low-diversity, Lactobacillus -dominated communities toward more taxonomically diverse, ARG-harbouring taxa. Increased redundancy was associated with higher microbial alpha diversity and enrichment of glycan-related metabolic pathways, particularly UDP-N-acetyl-D-glucosamine biosynthesis, a precursor pathway for glycan assembly. These microbial functional features correlated with host glycomic signatures in serum and urine. Mediation and path modelling analyses supported associations among resistome FR, predicted UDP-sugar pathway potential, host glycomic variation, and endocrine-related traits. Our findings identify resistome FR as a quantifiable ecological property of the vaginal microbiome that is associated with microbial metabolic capacity and host glycomic variation in endometriosis. Rather than acting as a direct driver, FR may serve as a marker of microbiome organisation that relates to host-associated phenotypes, providing a framework for understanding microbiome–glycome interactions in reproductive tract disease.