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Propolis effects on dysbiosis of polycystic ovarian syndrome (PCOS) induced Wistar rats


Introduction: Polycystic ovarian syndrome (PCOS) is an endocrinopathy that has two major risk factors, genetics and environment. Tremellen and Pearce proposed a new theory of Dysbiosis of Gut Microbiota (DOGMA) as an environmental factor that can modified by probiotics. Propolis acts as a probiotic in diabetic rats and has been proven to change gut microbiota dysbiosis. This study evaluated whether propolis extract can modify dysbiosis in PCOS animal models compared to metformin.

Methods: This was a post-test-only control group design randomized control trial with 30 Wistar rats divided into five groups: control, PCOS, PCOS with metformin, PCOS with propolis extract, and PCOS with metformin plus propolis extract. PCOS induced by daily 100 mg/ testosterone propionate injection intramuscularly for 28 days. The feces in the caecum were extracted after the rats were sacrificed and analyzed for Firmicutes/Bacteroides ratio, alpha diversity, and beta diversity.

Result: Firmicutes abundance in the control group was the lowest, and Bacteroidetes abundance was lowest in the propolis group, although it’s not significantly different. Between groups, Firmicutes/Bacteroidetes ratio, alpha diversity, and beta diversity were not significantly different. Testosterone concentration and preantral follicle count in the propolis and metformin groups improved compared to the PCOS group (p=0,01 and p=0,025, respectively).

Conclusion: Propolis cannot modify dysbiosis in PCOS-induced rats, but it reduces total testosterone concentration and preantral follicle counts.


  1. Chang JE. Polycystic Ovary Syndrom and Hyperandrogenic States. Yen and Jaffe’s Reproductive Endrocinology 7ed. 2014;485-511.
  2. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28-38. Available from:
  3. Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Baltimore: Lippincot Williams & Wilkins. 2011;495-531.
  4. Tremellen K, Pearce K. Dysbiosis of Gut Microbiota (DOGMA) – a novel theory for the developement of polycyctic ovarian syndrome. Med Hypotheses. 2012;79:104-12. Available from:
  5. He F, Li Y. Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: a review. J Ovarian Res. 2020;1–13. Available from:
  6. Rizk MG, Thackray VG. Intersection of polycystic ovary syndrome and the gut microbiome. J Endocr Soc. 2021;5(2):1–16. Available from:
  7. Stojanov S, Berlec A, Štrukelj B. The Influence of probiotics on the firmicutes/bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease. Microorganisms. 2020;8(1715):1-16. Available from:
  8. Xue M, Liu Y, Xu H, Zhou Z, Ma Y, Sun T, et al. Propolis modulates the gut microbiota and improves the intestinal mucosal barrier function in diabetic rats. Biomed Pharmacother. 2019;118(10939):1-13. Available from:
  9. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. International PCOS Network. Erratum. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2019;34(2):364-79. Available from:
  10. Pascale A, Marchesi N, Govoni S, Coppola A, Gazzaruso C. The role of gut microbiota in obesity, diabetes mellitus and effect of metformin: new insights into old diseases. Curr Opin Pharmacol. 2021;49:1–5. Available from:
  11. Siddiqui R, Makhlouf Z, Alharbi AM, Alfahemi H, Khan NA. The gut microbiome and female health. Biology. 2022;11:1-17. Available from:
  12. Čoklo M, Maslov DR, Kraljević Pavelić S. Modulation of gut microbiota in healthy rats after exposure to nutritional supplements. Gut Microbes. 2020;12(1):1-28. Available from:
  13. Magne F, Gotteland M, Gauthier L, Zazueta A, Pesoa S, Navarrete P, et al. The Firmicutes/Bacteroidetes ratio: a relevant marker of gut dysbiosis in obese patients? Nutrients. 2020;12:1-17. Available from:
  14. Wang K, Jin X, You M, Tian W, Leu RKL, Topping DL. Dietary propolis ameliorates dextran sulfate sodium induced colitis and modulates the gut microbiota in rats fed a western diet. Nutrients. 2017;9(8):1-13. Available from:
  15. Du Y, Zhu Y, Zhou Y, Ding J, Liu J. Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study. Mol Biomed. 2022;3(41):1-32. Available from:
  16. Petakh P, Kamyshna I, Kamyshnyi A. Effects of metformin on the gut microbiota: A systematic review. Mol Metab. 2023:1-8. Available from:
  17. Xue J, Li X, Liu P, Li K, Sha L, Yang X, et al. Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice. Endocr J. 2019;28;66(10):859-870. Available from:
  18. Lin W, Wen LY, Wen JP, Xiang GD. Effects of sleeve gastrectomy on fecal gut microbiota and short-chain fatty acid content in a rat model of polycystic ovary syndrome. Front. Endocrinol. 2021;12:1-14. Available from:
  19. Jobira B, Frank DN, Pyle L, Silveira LJ, Kelsey MM, Garcia-Reyes Y, et al. Obese adolescents with PCOS have altered biodiversity and relative abundance in gastrointestinal microbiota. J Clin Endocrinol Metab. 2020;105(6):e2134–44. Available from:
  20. Zhao, XX, Jiang YP, Xi HY, Chen L, Feng XL. Exploration of the relationship between gut microbiota and polycystic ovary syndrome (PCOS): a review. Geburtsh Frauenheilk. 2020;80:161–71. Available from:
  21. Qi X, Yun C, Pang Y, Qiao J. The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes. 2021;13(1):1-21. Available from:
  22. Sameni HR, Ramhormozi P, Bandegi AR, Taherian AA, Mirmohammadkhani M, Safari M. Effects of ethanol extract of propolis on histopathological changes and anti-oxidant defense of kidney in a rat model for type 1 diabetes mellitus. J. Diabetes Investig. 2016:7(4):506–513. Available from:
  23. Zheng Y, Wu Y, Tao L, Chen X, Jones TJ, Wang K, et al. Chinese propolis prevents obesity and metabolism syndromes induced by a high fat diet and accompanied by an altered gut microbiota structure in mice. Nutrients. 2020;12(4):1-23. Available from:
  24. Chien YH, Yu YH, Chen YW. Taiwanese green propolis ameliorates metabolic syndrome via remodeling of white adipose tissue and modulation of gut microbiota in diet-induced obese mice. Biomed Pharmacother. 2023;160:1-14. Available from:
  25. Ali A, Paramanya A, Poojari P, Arslan-Acaroz D, Acaroz U, Kostić AŽ. The utilization of bee products as a holistic approach to managing polycystic ovarian syndrome-related infertility. Nutrients. 2023;25;15(5):1-15. Available from:
  26. Zhao H, Xing C, Zhang J, He B. Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta‑analysis. Reprod Health. 2021;18(171):1-12. Available from:
  27. Bafrouei MH, Khazali H, Kalantar SM, Khoradmehr A. The comparative effect of Citrullus colocynthis hydro-alcoholic extract and metformin on morphometric ovarian follicles disorders in estradiol valerate induced-polycystic ovary syndrome rats. Galen Med J. 2018;11;7:e1045. Available from:
  28. Sapmaz T, Sevgin K, et al. Propolis protects ovarian follicular reserve and maintains the ovary against polycystic ovary syndrome (PCOS) by attenuating degeneration of zona pellucida and fibrous tissue. Biochem. Biophys. Rep. 2022;636(2):97-103. Available from:

How to Cite

Puspitasari, V. D., Lestari, E. S., & Pramono, N. (2024). Propolis effects on dysbiosis of polycystic ovarian syndrome (PCOS) induced Wistar rats . Bali Medical Journal, 13(1), 924–929.




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Vannya Dewi Puspitasari
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Endang Sri Lestari
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Noor Pramono
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