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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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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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]
In the citing paper
“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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Estrobolome: Is there a missing link?
Benagiano, G., Pluchino, N., Archer, D. F., & Stanczyk, F. Z. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.106967 · Cited by 5
The Gut Gambit: A Review of How Microbial Imbalance Fuels Metabolic Mayhem
Venkata, L. N. S., Mishra, A. K., Mohanta, Y. K., Rustagi, S., Bahuguna, A., Tomar, A., Baek, K.-H., & Mishra, B. (2026) · Nutrients · doi:10.3390/nu18060888 · Cited by 8
“The progression of NAFLD is more significantly influenced by subsequent processes [111].”
Beyond the reproductive tract: gut microbiome and its influence on gynecological health
Pérez‐Prieto, I., Rodríguez-Santisteban, A., & Altmäe, S. (2024) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/gco.0000000000000952 · Cited by 5
Wu, R., Mai, Z., Song, X., & Zhao, W. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1524521 · Cited by 5
Endometrial Receptivity in Patients with Polycystic Ovary Syndrome
Albu, A. I., & Albu, D. N. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.98624 · Cited by 5
Wang, B., Hu, L., & Dong, P. (2024) · SLAS TECHNOLOGY · doi:10.1016/j.slast.2024.100178 · Cited by 5
“A total of eight studies [18,25,26,33,39 – 42] encompassing 441 participants provided data on the relative abundances of different phyla at the microbial taxonomic level.”
InfluentialPolycystic Ovary Syndrome (PCOS)
Hechtman, L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-43044-9.00209-0 · Cited by 6
Temporal dynamics of gut microbiota in triclocarban-exposed weaned rats
Kennedy, R. C. M., Fling, R. R., Robeson, M. S., Saxton, A. M., Schneider, L. G., Darcy, J. L., Bemis, D. A., Zhao, L., & Chen, J. (2018) · Environmental Science and Pollution Research · doi:10.1007/s11356-018-1627-9 · Cited by 4
Linking altered gut microbiome to polycystic ovarian syndrome through immune mediated pathway
Pathak, V. A., Kshirsagar, S. J., & Deokar, G. S. (2025) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2025.104648 · Cited by 7
Yang, X., Luo, H., Li, Q., Zhu, W., Fu, L., Chen, L., Li, X., Su, H., Zhang, L., & Huang, Y. (2025) · The FASEB Journal · doi:10.1096/fj.202502661r · Cited by 4
Impact of Reducing Obesity in PCOS: Methods and Treatment Outcomes
Dzienny, A. C., & Seifer, D. B. (2025) · Journal of Personalized Medicine · doi:10.3390/jpm15110518 · Cited by 6
“Individuals with PCOS have also been found to show a hierarchical clustering of species that can distinguish samples from healthy controls [27,28].”
Uterine fibroids and endometrial microbiota: is there a relationship?
Adamyan, L. V., Priputnevich, T. V., Gavrilova, T. Y., & Grigorian, I. E. (2022) · Russian Journal of Human Reproduction · doi:10.17116/repro202228061164 · Cited by 4
Polycystic ovary syndrome: new and promising treatment methods
Муратовна, Г. Д., Sheremetyeva, E. V., Kalashnikova, M. F., Dzgoeva, F. K., & Алборова, Е. Т. (2024) · Problems of Endocrinology · doi:10.14341/probl13400 · Cited by 5
Huang, L., Huang, Y., & Pang, Q. (2022) · Pharmacological Research - Modern Chinese Medicine · doi:10.1016/j.prmcm.2022.100174 · Cited by 4
Chen, H., Tu, Y., Zhang, C., Li, J., Wu, T., Liu, S., He, L., Zhang, A., Li, Y., Lu, L. F., et al. (2023) · Trials · doi:10.1186/s13063-023-07825-9 · Cited by 4
Alessandri, G., Mancabelli, L., Fontana, F., Lepore, E., Forte, G., Burratti, M., Ventura, M., & Turroni, F. (2024) · Microbial Biotechnology · doi:10.1111/1751-7915.14540 · Cited by 6
Association of Gut Microbiota With Fatigue in Black Women With Polycystic Ovary Syndrome
Slack, J. E., Kosyakova, N., Pelkmans, J. L., Houser, M. C., Dunbar, S. B., Spencer, J. B., Ferranti, E. P., & Narapareddy, S. L. (2024) · Nursing Research · doi:10.1097/nnr.0000000000000788 · Cited by 4
“Recent research has suggestedapotentiallinkbetweenthegutmicrobiomeandPCOS, highlighting alterations in microbial composition and diversity (Lindheim et al., 2017).”
Microbiota and Estrogen Metabolism
Chen, J. H., Douglass, J., & Habibi, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819265-8.00069-3 · Cited by 4
Zhu, W., Fu, L., Xu, C., Peng, K., Liu, Y., Tang, H., Huang, Y., & Yang, X. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.978019 · Cited by 4
From Gut to Reproductive Health: Exploring Microbiome Interactions and Future Interventions
Singh, S., Kriti, M., Sharma, P., Pal, N., Sarma, D. K., Verma, V., Tiwari, R. R., & Kumar, M. (2025) · Reproductive Sciences · doi:10.1007/s43032-025-02001-7 · Cited by 3
“For instance, a study showed that phage therapy targeting Escherichia coli and Enterococcus faecalis helped restore hormonal balance and improved ovarian function in PCOS-induced rats [183].”
Yang, W., Yin, L., Xie, Q., Tan, M., Liu, Y., Xu, J., & Wu, J. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1699600 · Cited by 3
Bridging tradition and innovation: electroacupuncture’s impact on premature ovarian insufficiency
He, S., Ling, L., Sheng, Y., Zhao, X., Yuan, L. X., Liu, P., Li, B., & Zhang, B. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1685306 · Cited by 3
Pinton, P. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1787902 · Cited by 3
“The gut microbiome has emerged as a key mediator linking environmental inputs to metabolic and reproductive outcomes, with alterations in microbial composition and barrier function observed in individuals with PCOS (32).”
Banerjee, A. A., & Banerjee, A. G. (2024) · International Journal of Translational Medical Research and Public Health · doi:10.25259/ijtmrph_20_2024 · Cited by 3
Special Issue “New Challenges and Perspectives in Polycystic Ovary Syndrome”
Parker, J., & Hofstee, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062665 · Cited by 3
“Women with PCOS have decreased serum 17-beta-estradiol levels in the lower normal range but may have higher levels in the endometrium [31,32].”
Huang, X., Wu, L., Zhang, Y., Lai, X., & Sun, D. (2025) · Endocrine Connections · doi:10.1530/ec-25-0162 · Cited by 3
“Furthermore, it has also been found that the lower diversity of gut microbiota in PCOS patients, the destruction of the intestinal barrier, and the production of endotoxin may be related to the clinical phenotype of PCOS (74).”
Das polyzystische Ovar-Syndrom – Entstehung, Behandlung und neue Erkenntnisse
Borzan, V., Mayr, A., & Obermayer-Pietsch, B. M. (2021) · Journal für Klinische Endokrinologie und Stoffwechsel · doi:10.1007/s41969-021-00135-y · Cited by 3
Self-citationTrummer, O., Hoeller, J., Reintar, S., Tandl, V., Foessl, I., Borzan, V., Theiler‐Schwetz, V., Trummer, C., Lerchbaum, E., & Obermayer-Pietsch, B. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063205 · Cited by 4
“The pathogenesis of PCOS has not been fully understood, but it is assumed to be multifactorial, comprising genetics, the intrauterine environment, the microbiome and lifestyle factors such as diet, exercise or stress [2,6].”
Self-citationLokshin, V. N., Куценко, И. И., Олегович, Б. И., Bulgakova, V. P., Иосифовна, К. Е., Biryukova, M. I., Borovikova, O. I., & Nikogda, J. V. (2023) · Кубанский научный медицинский вестник · doi:10.25207/1608-6228-2023-30-5-15-40 · Cited by 2
Li, Z., Liu, Y., Wang, Y., Cai, Q., Wang, Y., Bai, Y., Liu, H., Xu, C., & Zhang, F. (2024) · Biology of Reproduction · doi:10.1093/biolre/ioae058 · Cited by 2
Veličković, N. A., Vratarić, M., Mićić, B., Teofilović, A., Radovanović, M., Ignjatović, S., Gašić, U., Djordjevic, A. D., Μacut, D., & Milutinović, D. V. (2025) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-025-01103-9 · Cited by 2
“Furthermore, the gut microbial community is directly involved in the regulation of testosterone production in female mice, linking the progression of hyperandrogenemia and hyperinsulinemia in PCOS with intestinal dysbiosis [25, 34].”
Zhang, Y., Chen, M., Zhou, Z. G., Guo, Y., Zheng, L., Yu, Y., Liu, J., Zhou, Y., Lu, H., Yao, S., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1517934 · Cited by 2
Gut–ovary axis and multiomic insights into PCOS in a DHEA-induced rat model
Chen, Z., Lu, Q., Lin, A., Tan, M., Li, W., Tang, S., Feng, J., Hou, C., Zhu, Y., Xu, M., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-30862-0 · Cited by 2
Li, Q., Wu, Y., Chen, L., & Wang, R. (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00703-w · Cited by 2
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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