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. 2025 Aug 7.
doi: 10.1007/s00125-025-06509-0. Online ahead of print.

Adverse pregnancy outcomes in women with type 1 diabetes are associated with multiple alterations in the vaginal microbiome

Alexandra J Roth-Schulze  1   2 , Esther Bandala-Sanchez  1   2 , Katrina M Ngui  1   2 , Gaetano Naselli  1   2 , Helena Oakey  3 , Patricia Ashwood  3 , Guinevere Martin  3 , James D Brown  3 , Enrique Zozaya-Valdés  1   2 , Rebecca L Thomson  3 , Peter G Colman  4 , John M Wentworth  1   2   4 , Peter J Vuillermin  5   6 , Tony Hunyh  7   8 , Georgia Soldatos  9   10 , Jennifer J Couper  3 , Megan A S Penno  3 , Leonard C Harrison  11   12 ; ENDIA Study Group
Affiliations

Adverse pregnancy outcomes in women with type 1 diabetes are associated with multiple alterations in the vaginal microbiome

Alexandra J Roth-Schulze et al. Diabetologia. .

Abstract

Aims/hypothesis: The vaginal microbiome has been linked to adverse pregnancy outcomes, which are markedly increased in women with type 1 diabetes. To investigate this relationship, we profiled the vaginal microbiome in pregnant women with and without type 1 diabetes, and in relation to pre-term birth (PTB) and pre-eclampsia (PE) in women with type 1 diabetes.

Methods: Bacterial and fungal microbiomes were analysed by 16S rRNA gene and internal transcribed spacer 1 sequencing, respectively, in the third trimester of 310 pregnancies (160 with type 1 diabetes) for bacteria, and 147 pregnancies (70 with type 1 diabetes) for fungi.

Results: The vaginal microbiome was altered by type 1 diabetes in pregnancy, with an increase in the bacterial species Lactobacillus iners and Lactobacillus jensenii, and in the anaerobic genera Gardnerella, Anaerococcus, Prevotella, Dialister, Peptoniphilus and others that are associated with vaginal dysbiosis. In addition, the abundance of the fungal species Malassezia restricta was increased in women with type 1 diabetes. These changes were associated with increased risks of PTB and PE. PTB was associated with higher bacterial alpha diversity, decreased abundance of Lactobacillus reuteri, and increased abundance of Malassezia fungal genus, family Malasseziaceae and order Malasseziales. PE was associated with higher bacterial alpha diversity, increased abundance of Gardnerella vaginalis and decreased abundance of Candida albicans.

Conclusions/interpretation: Adverse pregnancy outcomes in women with type 1 diabetes are reflected by distinct changes in the vaginal microbiome. This highlights the importance of monitoring and managing the vaginal microbiome in high-risk pregnancies, particularly those complicated by type 1 diabetes. Early detection and treatment of risk-associated taxa, e.g. G. vaginalis in the case of PE, could potentially improve vaginal health and pregnancy outcomes in women with type 1 diabetes.

Keywords: Candida; Gardnerella vaginalis; Malassezia; 16S rRNA gene; Community state types; ITS1; Internal transcribed spacer 1; Lactobacilli; Microbiome; Mycobiome; Pre-eclampsia; Pre-term birth; Pregnancy; T1D; Type 1 diabetes.

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Conflict of interest statement

Acknowledgements: The authors thank S. A. Wilcox (Genomics Hub, Walter and Eliza Hall Institute of Medical Research) for advice with DNA sequencing and D. Huang for processing samples. We also gratefully acknowledge the participants and their families who contribute to the ENDIA Study. Data availability: The demultiplexed raw sequencing data supporting the findings of this study are publicly available in the NCBI Sequence Read Archive (SRA; https://www.ncbi.nlm.nih.gov/sra ) under project number PRJNA1037097. Code availability: All code used in the analyses is available on GitHub at https://github.com/RothSchulze/Adverse-pregnancy-outcomes-in-women-with-T1D-and-vaginal-microbiome , commit 8241215 (archived version used for this analysis). The repository includes Qiime2 command logs for sequence processing, R Markdown scripts and the associated R objects containing taxonomic profiles and metadata used for statistical analyses. Funding: Open Access funding enabled and organized by CAUL and its Member Institutions. This research was supported by Breakthrough T1D (formerly known as JDRF) Australia, a Commonwealth of Australia grant for Accelerated Research under the Medical Research Future Fund, and funding from the Leona M. and Harry B. Helmsley Charitable Trust (grant key 3-SRA-2020-966-M-N). In addition, support was provided by the National Health and Medical Research Council of Australia (NHMRC) Centre of Research Excellence for the Protection of Pancreatic Beta Cells (1078106) and JDRF International (1-SRA-2018-543-S-B). Additional support was provided by an NHMRC program grant (LCH 1037321), the Victorian State Government Operational Infrastructure Support, Diabetes South Australia, and the NHMRC Research Institute Infrastructure Support Scheme. LCH was supported by a NHMRC leadership investigator grant (APP1173945). Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: AJR-S performed bioinformatic analyses under the supervision of LCH and wrote the manuscript with LCH; EB-S performed DNA extraction and fungal sequencing and discussed the manuscript; KMN performed DNA extraction and sequencing and discussed the manuscript; GN performed DNA extraction and fungal sequencing; HO prepared maternal summary tables, advised on statistical analysis, and discussed and edited the manuscript; PA prepared maternal summary tables; GM analysed data. JDB prepared maternal summary tables; EZ-V contributed to bioinformatic analysis and discussion; RLT analysed dietary and physical activity data; PGC, JMW, GS and TH contributed to participant recruitment and sample collection; PJV contributed to study design, recruitment and sample collection; JJC contributed to participant recruitment and sample collection, and discussed and edited the manuscript; MASP contributed to study conception and design, compiled metadata and edited the manuscript; and LCH designed and supervised the study, analysed data and wrote the manuscript with AJR-S. All authors reviewed the draft manuscript and approved the final version of the manuscript. LCH is responsible for the integrity of the work as a whole and is the guarantor of the work.

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