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Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study
Open accessAbstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female endocrinopathy of unclear origin characterized by hyperandrogenism, oligo-/anovulation, and ovarian cysts. Women with PCOS frequently display overweight, insulin resistance, and systemic low-grade inflammation. We hypothesized that endotoxemia resulting from a leaky gut is associated with inflammation, insulin resistance, fat accumulation, and hyperandrogenemia in PCOS. In this pilot study, we compared the stool microbiome, gut permeability, and inflammatory status of women with PCOS and healthy controls. METHODS: 16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls. Data processing and microbiome analysis were conducted in mothur and QIIME using different relative abundance cut-offs. Gut barrier integrity, endotoxemia, and inflammatory status were evaluated using serum and stool markers and associations with reproductive, metabolic, and anthropometric parameters were investigated. RESULTS: The stool microbiome of PCOS patients showed a lower diversity and an altered phylogenetic composition compared to controls. We did not observe significant differences in any taxa with a relative abundance>1%. When looking at rare taxa, the relative abundance of bacteria from the phylum Tenericutes, the order ML615J-28 (phylum Tenericutes) and the family S24-7 (phylum Bacteroidetes) was significantly lower and associated with reproductive parameters in PCOS patients. Patients showed alterations in some, but not all markers of gut barrier function and endotoxemia. CONCLUSION: Patients with PCOS have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters. Gut barrier dysfunction and endotoxemia were not driving factors in this patient cohort, but may contribute to the clinical phenotype in certain PCOS patients.
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“Similar to microbiomes associated with obesity, the microbiomes of individuals with PCOS have generally been found to have lower alpha diversity (lower numbers of bacterial taxa) than controls, and most studies describe an altered composition of taxa relative to controls [140,143].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [143]
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“Although most studies are small, dysbiosis has consistently been found to correlate with different physiological parameters, such as obesity, sex hormones and metabolic defects [140,141,143].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [143]
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“Dysbiosis is a consistent finding when looking at the microbiome of women with PCOS [140,141,142,143].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [143]
Experimental — accuracy not yet measuredIn the citing paper
“Alternative mechanisms of the pathogenesis of prediabetes and T2D in subjects with PCOS are muscle mitochondrial dysfunction [28] and the gut microbiome [29].”
From From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management (2020) · cites this paper as [29]
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“However, all diets that aim to reduce weight are considered beneficial [29].”
From From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management (2020) · cites this paper as [29]
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“Distinct microbiome patterns have also been noted across PCOS subgroups, such as increased Prevotella in hyperandro-genic phenotypes [31, 32].”
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Escalona-Nández, I., Palacios‐González, B., Estanes-Hernández, A., Guevara‐Cruz, M., Torre, A., Granados-Arreola, J., Vera, I., Noriega, L. G., & Pérez‐Monter, C. (2025) · Nutrition · doi:10.1016/j.nut.2025.112915
Exploring the interactions of gut microbiome and metabolites in polycystic ovary syndrome: a review
Li, J., Jia, Y., Xu, H., Bing, H., Ling, Q., Wang, S., Wang, Y., Zhang, X., & Zhao, L. (2025) · Microbiological Research · doi:10.1016/j.micres.2025.128309 · Cited by 1
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Exploring the Role of Abnormal Qi Movement in Polycystic Ovary Syndrome Based on the Gut-Brain Axis
高, 惠. (2025) · Advances in Clinical Medicine · doi:10.12677/acm.2025.15113141
Zhang, M., Liu, D., Lv, S., Wang, C., & Jiao, H. (2025) · Scientific Reports · doi:10.1038/s41598-025-23395-z
“…by elevated levels of inflammatory markers such as hs-CRP and IL-6 64 , and the upregulation of inflammation leads to an increase in lipid storage 65 , which promotes obesity and visceral fat accumulation, leading to metabolic disturbances 66 such as increased levels of triglycerides and…”
Fan, H., Hong, X., Zeng, J., Wang, X., & Chen, J. (2021) · Figshare · doi:10.6084/m9.figshare.14992996
Riviere, A. J., Smith, K. S., Schaberg, M. N., Greene, M. W., & Frugé, A. D. (2022) · Figshare · doi:10.6084/m9.figshare.19589193
Riviere, A. J., Smith, K. S., Schaberg, M. N., Greene, M. W., & Frugé, A. D. (2022) · Figshare · doi:10.6084/m9.figshare.19589181
Mayneris‐Perxachs, J., Arnoriaga‐Rodríguez, M., Luque-Córdoba, D., Priego‐Capote, F., Pérez-Brocal, V., Moya, A., Burokas, A., Maldonado, R. J., & Fernández-Real, J.-M. (2020) · Figshare · doi:10.6084/m9.figshare.12981212
Riviere, A. J., Smith, K. S., Schaberg, M. N., Greene, M. W., & Frugé, A. D. (2022) · Figshare · doi:10.6084/m9.figshare.19589199
Mayneris‐Perxachs, J., Arnoriaga‐Rodríguez, M., Luque-Córdoba, D., Priego‐Capote, F., Pérez-Brocal, V., Moya, A., Burokas, A., Maldonado, R. J., & Fernández-Real, J.-M. (2020) · Figshare · doi:10.6084/m9.figshare.12981224
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Riviere, A. J., Smith, K. S., Schaberg, M. N., Greene, M. W., & Frugé, A. D. (2022) · Figshare · doi:10.6084/m9.figshare.19589184
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Gut and Vaginal Microbiome Dysbiosis in PCOS
Kottahachchi, D., Subasinghe, C., & Bajaj, S. (2025) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9798898810931125010021
A Roadmap for Advancing Women's Health in Disorders of the Gut‐Brain Interaction
Heath, M. R., & Luo, Y. (2025) · United European Gastroenterology Journal · doi:10.1002/ueg2.70167
Characteristic Gut Microbiota in PCOS-IR Patients and Its Association with Endocrine Features
Liang, W., Yao, Y., Ren, X., Anran, X. U. E., Cai, M., Yu, J., Yu, C., Zhou, L., & Zhai, D. (2025) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s561487
“23 The abundance of this phylum showed a significant negative correlation with HOMA-IR, suggesting its potential role in modulating insulin sensitivity through metabolic pathways.”
Kulkarni, N., Jalan, S. K., & Kumar, V. (2025) · International Conference on Computing, Communication and Automation · doi:10.1109/iccca66364.2025.11325458
“Advances in sequencing, metabolomics, and computational biology have clarified how dysbiosis contributes to both local and systemic disease processes [1], [2].”
Nanoparticles in Polycystic Ovary Syndrome Therapy: Unveiling New Horizons in Reproductive Health
Joshi, D., Shukla, P., & Choudhary*, D. N. K. (2025) · International Journal of Newgen Research in Pharmacy & Healthcare · doi:10.61554/ijnrph.v3i2.2025.180
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Advances in the Role of Endometrial Microbiota Alterations in the Pathogenesis of Endometriosis
Xu, Z., Guo, W., & Shen, Y. (2026) · Reproductive Sciences · doi:10.1007/s43032-026-02050-6
Therapeutic Application of Postbiotics in the Management of Polycystic Ovarian Syndrome
Pathak, V. A., Kshirsagar, S. J., Deokar, G. S., Anyimadu, C. F., Sangsawad, P., Li, L., Abass, K. S., & Nirmal, N. P. (2026) · ACS Nutrition Science · doi:10.1021/acsnutrsci.5c00042
Состав кишечной микробиоты и эндокринно-метаболические нарушения при синдроме поликистозных яичников
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Role of Gut Microbiota in Menstrual Dysregulation in Polycystic Ovary Syndrome
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“Research has shown a loss of microbial diversity in PCOS patients with a reduction in Bacteroidetes and increase in Firmicutes, which is related to insulin resistance and hyperandrogenism [10].”
Suturina, L., Belkova, N. L., Sidorova, T. V., Евгеньевна, С. Н., Igumnov, I., Lazareva, L., Николаевна, Д. И., Nadeliaeva, I. G., Sholokhov, L. F., Belenkaia, L. V., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27072974
“These authors described such taxa as bacteria from order ML615J-28 (phylum Mycoplasmatota) and family S24-7 (phylum Bacteroidota) [3].”
InfluentialShibah, S. R. M. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.6486878
THE ROLE OF GUT MICROBIOTA IN THE PATHOGENESIS OF POLYCYSTIC OVARY SYNDROME
Stępień, A., Podleśna, M., Bączek, K., Chromiak, K., Curzytek, K., Bluczak, K., Czechowicz, K., Radziwiłko, J. M., Pastuszak, A., & Kozińska, A. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.1(49).2026.4524
Metabolic aspects of polycystic ovary syndrome
Pappas, D., Kandaraki, E., Kalogirou, A., & Diamanti‐Kandarakis, E. (2026) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2026.2656240
“Women with PCOS consistently demonstrate reduced microbial diversity, altered bacterial composition, and shifts in microbial metabolite production compared with metabolically matched controls [63–65].”
VAGINAL MICROBIOME ALTERATIONS IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME
Makulec, G., Zienkiewicz, D., Domosud, K., Kostro, J. M., Novik, L., Kozicki, M. J., Libera, A., Bartkiewicz, K., & Jędra, Z. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.2(50).2026.5079
Huang, Q.-P., Huang, L.-Y., Liao, G.-L., Huang, C.-X., Wang, K.-Y., Xu, J., Sun, H.-R., Jiang, T., & Song, J.-L. (2026) · Food Bioscience · doi:10.1016/j.fbio.2026.108995
Li, Y. Y., He, F.-F., Donge‐Liu, Bin‐Xu, & Shuyi‐Li (2026) · Health Science Reports · doi:10.1002/hsr2.72593
ASSOCIATION BETWEEN INTESTINAL ZONULIN EXPRESSION AND POLYCYSTIC OVARY SYNDROME IN RATS
Usman, F., Saleh, M. I., Effendi, K. Y., Lestari, P. M., Widjiati, W., & Stevanny, B. (2026) · Archives of Veterinary Medicine · doi:10.46784/e-avm.v19i1.510
“These experimental findings are consistent with clinical observations reporting elevated zonulin in women with PCOS and its correlation with metabolic dysfunction (Zhang et al., 2015; Lindheim et al., 2017).”
Tunjungseto, A., Hadi, O. A., Pratiwi, I. W., Iffatunnisa, F., Ahsan, F., & Santoso, B. (2026) · Diagnostics · doi:10.3390/diagnostics16132041
Toll-like receptor 4 knockout mice are protected against PMOS-like pathogenesis
Wiggins, K. D., Mundo, Z. D. D., Angulo, J. A. A., Naidu, N., Saba, A., Zhou, L., Garcia, C., Nguyen, C. M., Ujagar, N. S., Torre, J.-J. D. L., et al. (2026) · Reproduction · doi:10.1093/reprod/xaag081
Metadata
- Authors
- Lindheim, L., Bashir, M., Münzker, J., Trummer, C., Zachhuber, V., Leber, B., Horvath, A., Pieber, T. R., Gorkiewicz, G., Stadlbauer, V., & Obermayer-Pietsch, B.
- Affiliations
- Medical University of Graz (AT)
- University of Graz (AT)
- Corresponding author
- Lindheim, Lisa
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-01-03
- Volume
- 12
- Issue
- 1
- Pages
- e0168390
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5207627
- OpenAlex
- W2568515092
- Cited by
- 416
- References
- 50
- Citations by year
- 2026: 51 · 2025: 43 · 2024: 55 · 2023: 70 · 2022: 52 · 2021: 56 · 2020: 44 · 2019: 23 · 2018: 18 · 2017: 3
- FWCI
- 27.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Austrian Science Fund (W1241)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- polycystic ovary syndrome, gut microbiota, intestinal barrier, endotoxemia, intestinal permeability, microbial diversity, Tenericutes, Bacteroidetes, S24-7, inflammation, insulin resistance, hyperandrogenemia, reproductive disorders, metabolic defects
- MeSH terms
- Gastrointestinal Microbiome, Adult, Anthropometry, Feces, Female, Humans, Inflammation, Tenericutes, Pilot Projects, Polycystic Ovary Syndrome, Surveys and Questionnaires, RNA, Ribosomal, 16S, Case-Control Studies, Principal Component Analysis, Bacteroidetes, Real-Time Polymerase Chain Reaction
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