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

In: npj Biofilms and Microbiomes · 2026 · doi:10.1038/s41522-026-01100-w · W7170074229
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This study found increased vaginal resistome functional redundancy in moderate/severe endometriosis, linking higher microbial diversity and glycan biosynthesis to host glycomic variation.

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Abstract

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.
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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. Similar content being viewed by others

Acknowledgements

We would like to thank all the participants who were involved in the study for their generous time and engagement. Zhe Pan has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 101034270. The endometriosis cohort has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 843862, H2020-MSCA-IF-2018. Author information Authors and Affiliations Corresponding authors Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary information Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. About this article Cite this article Pan, Z., Glover, L., Reidy, F. et al. Vaginal resistome redundancy is associated with microbial metabolic potential and host glycomic features in endometriosis. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-01100-w Received: Accepted: Published: DOI: https://doi.org/10.1038/s41522-026-01100-w

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