Lightning Talks 31st Annual Lorne Proteomics Symposium 2026

Copper intrauterine device (IUD) use associates with metaproteomic signatures of genital inflammation, altered epithelial barrier function, and microbial dysbiosis in South African women   (133187)

Nina Radzey 1 , Tariq Ganief 2 3 , Andrea Abrahams 2 , Rushil Harryparsad 4 , Bahiah Meyer 4 , Pai Lien Chen 5 , Celia Mehou-Loko 4 , Florence Lefebvre d'Hellencourt 5 , Gregory Buck 6 , Jennifer Smit 7 , Jerome Strauss 8 , Khatija Ahmed 9 10 , Mags Beksinska 7 , Myrna Serrano 6 , Veronique Bailey 9 , Charles Morrison 11 , Jennifer Deese 12 , Kavita Nanda 5 , Jonathan Blackburn 2 3 , Lindi Masson 1 3 13 14
  1. Women's, Children's and Adolescent's Health and Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
  2. Integrative Biomedical Sciences (IBMS), University of Cape Town, Cape Town, Western Cape, South Africa
  3. Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, Western Cape, South Africa
  4. Pathology, University of Cape Town, Cape Town, Western Cape, South Africa
  5. FHI 360, Durham, North Carolina, United States
  6. Microbiology and Immunology, Center for Microbiome Engineering and Data Analysis, Virginia Commonwealth University, Richmond, Virginia, United States
  7. MatCH Research Unit (MRU), Department of Obstetrics and Gynaecology, University of the Witwatersrand, Durban, Kwazulu-Natal, South Africa
  8. Obstetrics and Gynaecology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  9. Setshaba Research Centre, Tshwane, South Africa
  10. Paediatrics & Child Health, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, Gauteng, South Africa
  11. Independent Consultant, Chapel Hill, North Carolina, United States
  12. Consultant (formerly FHI360), Chapel Hill, North Carolina, United States
  13. Centre for the AIDS Programme of Research in South Africa, Durban, Kwazulu-Natal, South Africa
  14. Central Clinical School, Monash University, Melbourne, Victoria, Australia

Introduction: The effects of contraceptives on female genital tract host immunity and microbiota, two factors closely linked to sexual and reproductive health outcomes, remain to be defined. This study assessed the impact of three contraceptives on vaginal metaproteome profiles in South African women.

Methodology: We analysed the vaginal metaproteomes of 151 women in a sub-study of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomized to copper intrauterine device (IUD; n=51), depot medroxyprogesterone acetate (DMPA-IM; n=46), or levonorgestrel (LNG) implant (n=54) and vaginal swab samples were collected at baseline and 3 months post-initiation (M3). Data were generated using data-independent acquisition mass spectrometry and processed with DIA-NN (Data Independent Acquisition by Neural Networks), using a study-specific, in-silico library informed by existing, sample-matched 16S rRNA gene sequence data, literature and the human proteome. 16S rRNA gene sequencing microbiome groupings and sexually transmitted infection diagnostic results were used for quality control analysis of metaproteomic taxonomic data and to inform filtering thresholds. Gene Ontology via UniProt was used for protein functional annotation. The limma package in R was used to identify differentially expressed proteins and functions between baseline and M3 in each arm.

Results: The filtered dataset contained 3717 proteins (1875 human, 1842 microbial). Metaproteomic taxonomic profiles were broadly comparable to 16S gene sequencing data, but differences in the relative abundance of some microbial taxa were observed between methods. For example, Gardnerella vaginalis and Prevotella species were more abundant in the proteomic dataset. Women with non-optimal microbiome types had increased vaginal inflammation at baseline. DMPA-IM and LNG implant use were not associated with significant vaginal host or microbial proteome changes at M3 versus baseline. Copper IUD use associated with increased relative abundance of host proteins involved in immune and inflammatory responses, complement pathway activation, and altered epithelial barrier function at M3 versus baseline. Additionally, copper IUD use associated with unfavourable microbiome changes, including decreased relative abundance of optimal Lactobacillus species. However, microbiome type and Lactobacillus species relative abundance did not significantly modify the effect of copper IUD initiation on immune or epithelial signatures in linear regression models. This suggests the effects of copper IUD use on host inflammatory responses may not be entirely dependent on changes in the microbiome.

Conclusion: Copper IUD use was associated with host and microbiome changes previously linked to adverse reproductive outcomes. These findings inform contraceptive recommendations, choice and future product development, particularly in high-risk populations.