Polycystic ovary syndrome and gut microbiota


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disease. Its frequency varies from 6 to 19.9%, depending on the diagnostic criteria used. PCOS is associated with a high risk of type 2 diabetes and cardiovascular disease. The mechanisms for its development are not fully clear; therefore, the relevant issue is to search for the new components of the pathogenesis of the disease, which may predict the development of the pathological process, as well as the predictors for the efficiency of the prescribed therapy. The review presents recent studies establishing an association between the impaired gut microbial composition and the metabolic and clinical manifestations of PCOS. It is supposed that gut dysbiosis may be a potential pathogenetic factor in the development of PCOS, whereas normalization of the gut microbiota may improve the hormonal and metabolic prof iles in these patients. The imbalance of useful and harmful intestinal bacteria can lead to increased intestinal wall permeability and the release of toxins into the bloodstream, which causes chronic subclinical inflammation that contributes to the development of insulin resistance, followed by androgen hyperproduction, impaired folliculogenesis, and the development of PCOS. This review considers the new approaches to treating the syndrome, which are aimed at correcting the gut microbiota, subsequently normalizing the hormonal balance, insulin resistance, and restoring the rhythm of menstruation.

Full Text

Restricted Access

About the authors

Galina E. Chernukha

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: c-galinal@yandex.ru
Dr. Med. Sci., Professor, Head of the Department of Gynecological Endocrinology

Ekaterina D. Miroshina

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: emiroshina.md@gmail.com
postgraduate student, Department of endocrinological gynecology

Tatiana V. Priputnevich

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: priputl@gmail.com
Dr. Med. Sci., Head of the Microbiology, Clinical Pharmacology and Epidemiology Department

References

  1. Escobar-Morreale H.F. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat. Rev. Endocrinol. 2018; 14(5): 270-84. https://dx.doi. org/10.1038/nrendo.2018.24.
  2. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril. 2004; 81(1): 19-25. https://dx.doi. org/10.1016/j.fertnstert.2003.10.004.
  3. Dilbaz B., Cinar M., Ozkaya E., Tonyali N., Dilbaz S. Health related quality of life among different PCOS phenotypes of infertile women. J. Turk. Ger. Gynecol. Assoc. 2012; 13(4): 247. https://dx.doi.org/10.5152/jtgga.2012.39.
  4. Moghetti P. Insulin resistance and polycystic ovary syndrome. Curr. Pharm. Des. 2016; 22(36): 5526-34. https://dx.doi.org/10.2174/1381612822666160720155855.
  5. Chen L., Xu W.M., Zhang D. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome. Fertil. Steril. 2014; 102(4): 1167-74. https://dx.doi.org/10.1016/j. fertnstert.2014.06.027.
  6. Fauser B.C., Tarlatzis B.C., Rebar R.W., Legro R.S., Balen A.H., 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. e25. https://dx.doi.org/10.1016/ j.fertnstert.2011.09.024.
  7. Escobar-Morreale H.F. Reproductive endocrinology: Menstrual dysfunction--a proxy for insulin resistance in PCOS? Nat. Rev. Endocrinol. 2014; 10(1): 10-1. https://dx.doi.org/10.1038/nrendo.2013.232.
  8. Ferreira C.M., Vieira A.T., Vinolo M.A., Oliveira FA., Curi R., Martins Fdos S. The central role of the gut microbiota in chronic inflammatory diseases. J. Immunol. Res. 2014; 2014: 689492. https://dx.doi.org/10.1155/2014/ 689492.
  9. Tremellen K., Pearce K. Dysbiosis of gut microbiota (DOGMA)-a novel theory for the development of polycystic ovarian syndrome. Med. Hypotheses. 2012; 79(1): 104-12. https://dx.doi.org/10. 1016/j.mehy.2012.04.016.
  10. Quigley E.M. Basic definitions and concepts: organization of the gut microbiome. Gastroenterol. Clin. North Am. 2017; 46(1): 1-8. https://dx.doi.org/10.1016/j. gtc.2016.09.002.
  11. Sender R., Fuchs S., Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016; 14(8): e1002533. https://dx.doi. org/10.1371/journal.pbio.1002533.
  12. Neish A.S. Microbes in gastrointestinal health and disease. Gastroenterology. 2009; 136(1): 65-80. https://dx.doi.org/10.1053/j.gastro.2008.10.080.
  13. Tamburini S., Shen N., Wu H.C., Clemente J.C. The microbiome in early life: implications for health outcomes. Nat. Med. 2016; 22(7): 713-22. https://dx.doi. org/10.1038/nm.4142.
  14. Mshvildadze M., Neu J. The infant intestinal microbiome: friend or foe? Early Hum. Dev. 2010; 86(Suppl. 1): 67-71. https://dx.doi.org/10.1016/j. earlhumdev.2010.01.018. Erratum in Early Hum. Dev. 2014; 90(3): 163-4.
  15. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012; 486(7402): 207-14. https://dx.doi. org/10.1038/nature11234.
  16. Ley R.E., Turnbaugh PJ., Klein S., Gordon J.I. Microbial ecology: human gut microbes associated with obesity. Nature. 2006; 444(7122): 1022-3. https://dx.doi. org/10.1038/4441022a.
  17. Burger-van Paassen N., Vincent A., Puiman P.J., van der Sluis M., Bouma J., Boehm G. et al. The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection. Biochem. J. 2009; 420(2): 211-9. https://dx.doi.org/10.1042/BJ20082222.
  18. Maslowski K.M., Vieira AT., Ng A., Kranich J., Sierro F., Yu D. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009; 461(7268): 1282-6. https://dx.doi.org/10.1038/ nature08530.
  19. Le Chatelier E., Nielsen T., Qin J., Prifti E., Hildebrand F., Falony G. et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013; 500(7464): 541-6. https://dx.doi.org/10.1038/ nature12506.
  20. Дзгоева Ф. Х., Егшатян Л. В. Кишечная микробиота и сахарный диабет типа 2. Эндокринология: новости, мнения, обучение. 2018; 7(3): 55-63. [Dzgoeva F.Kh., Yegshatyan L.V. Intestinal microbiota and type 2 diabetes mellitus. Endocrinology: News. Opinions. Training. 2018; 7(3): 55-63. (in Russian)]. https://dx.doi.org/10.24411/2304-9529-2018-13005.
  21. Lindheim L., Bashir M., MUnzker J., Trummer C., Zachhuber V., Leber B. et al. 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. PLoS One. 2017; 12(1): e0168390. https://dx.doi.org/10.1371/journal.pone.0168390.
  22. Zhou L., Ni Z, Cheng W., Yu J., Sun S., Zhai D. et al. Characteristic gut microbiota and predicted metabolic functions in women with PCOS. Endocr. Connect. 2020; 9(1): 63-73. https://dx.doi.org/10.1530/EC-19-0522.
  23. Lim M.Y., You H.J., Yoon H.S., Kwon B., Lee J.Y., Lee S. et al. The effect of heritability and host genetics on the gut microbiota and metabolic syndrome. Gut. 2017; 66(6): 1031-8. https://dx.doi.org/10.1136/gutjnl-2015-311326.
  24. Liu R., Zhang C., Shi Y., Zhang F., Li L., Wang X. et al. Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome. Front. Microbiol. 2017; 8: 324. https://dx.doi.org/10.3389/ fmicb.2017.00324.
  25. Goodrich J.K., Waters J.L., Poole A.C., Sutter J.L., Koren O., Blekhman R. et al. Human genetics shape the gut microbiome. Cell. 2014; 159(4): 789-99. https:// dx.doi.org/10.1016/j.cell.2014.09.053.
  26. Sze M.A., Schloss P.D. Looking for a signal in the noise: revisiting obesity and the microbiome. mBio. 2016; 7(4): e01018-16. https://dx.doi.org/10.1128/ mBio.01018-16. Erratum in mBio. 2017 Dec 5; 8(6).
  27. Walters W.A., Xu Z., Knight R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett. 2014; 588(22): 4223-33. https://dx.doi. org/10.1016/j.febslet.2014.09.039.
  28. Lozupone C.A., Stombaugh J., Gonzalez A., Ackermann G., Wendel D., Vazquez-Baeza Y. et al. Meta-analyses of studies of the human microbiota. Genome Res. 2013; 23(10): 1704-14. https://dx.doi.org/10.1101/gr.151803.112.
  29. Thackray V.G. Sex, microbes, and polycystic ovary syndrome. Trends Endocrinol. Metab. 2019; 30(1): 54-65. https://dx.doi.org/10.1016/j.tem.2018.11.001.
  30. Vrieze A., Van Nood E., Holleman F., Salojarvi J., Kootte R.S., Bartelsman J.F. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012; 143(4): 913-6. e7. https://dx.doi.org/10.1053/j.gastro.2012.06.031. Erratum in Gastroenterology. 2013; 144(1): 250.
  31. Larsen N., Vogensen F.K., van den Berg F.W., Nielsen D.S., Andreasen A.S., Pedersen B.K. et al. Gut microbiota in human adults with type 2 diabetes differs from nondiabetic adults. PLoS One. 2010; 5(2): e9085. https://dx.doi.org/10.1371/journal. pone.0009085.
  32. Guo Y., Qi Y., Yang X., Zhao L., Wen S., Liu Y., Tang L. Association between polycystic ovary syndrome and gut microbiota. PloS One. 2016; 11(4): e0153196. https://dx.doi.org/10.1371/journal.pone.0153196.
  33. Kelley S.T., Skarra D.V., Rivera A.J., Thackray V.G. The gut microbiome isaltered in a letrozole-induced mouse model of polycystic ovary syndrome. PLoS One. 2016; 11(1): e0146509. https://dx.doi.org/10.1371/journal.pone.
  34. Kauffman A.S., Thackray V.G., Ryan G.E., Tolson K.P., Glidewell-Kenney C.A., Semaan S.J. et al. A novel letrozole model recapitulates both the reproductive and metabolic phenotypes of polycystic ovary syndrome in female mice. Biol. Reprod. 2015; 93(3): 69. https://dx.doi.org/10.1095/ biolreprod.115.131631.
  35. Skarra D.V., Hernandez-Carretero A., Rivera A.J., Anvar A.R., Thackray V.G. Hyperandrogenemia induced by letrozole treatment of pubertal female mice results in hyperinsulinemia prior to weight gain and insulin resistance. Endocrinology. 2017; 158(9): 2988-3003. https://dx.doi.org/10.1210/en.2016-1898.
  36. Knights D., Silverberg M.S., Weersma R.K., Gevers D., Dijkstra G., Huang H. et al. Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med. 2014; 6(12): 107. https://dx.doi.org/10.1186/ s13073-014-0107-1.
  37. Torres P.J., Siakowska M., Banaszewska B., Pawelczyk L., Duleba A.J., Kelley S.T., Thackray V.G. Gut microbial diversity in women with polycystic ovary syndrome correlates with gyperandrogenism. J. Clin. Endocrinol. Metab. 2018; 103(4): 1502-11. https://dx.doi.org/10.1210/jc.2017-02153.
  38. Zhang J., Sun Z., Jiang S., Bai X., Ma C., Peng Q. et al. Probiotic Bifidobacterium lactis V9 regulates the secretion of sex hormones in polycystic ovary syndrome patients through the gut-brain axis. mSystems. 2019; 4(2): e00017-19. https:// dx.doi.org/10.1128/mSystems.00017-19.
  39. Finucane M.M., Sharpton T.J., Laurent T.J., Pollard K.S. A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter. PLoS One. 2014; 9(1): e84689. https://dx.doi.org/10.1371/journal.pone.0084689.
  40. Cani P.D., Bibiloni R., Knauf C., Waget A., Neyrinck A.M., Delzenne N.M., Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008; 57(6): 1470-81. https://dx.doi.org/10.2337/db07-1403.
  41. Insenser M., Murri M., Del Campo R., Martinez-Garcia M.A., Fernandez-Duran E., Escobar-Morreale H.F. Gut microbiota and the polycystic ovary syndrome: influence of sex, sex hormones, and obesity. J. Clin. Endocrinol. Metab. 2018; 103(7): 2552-62. https://dx.doi.org/10.1210/ jc.2017-02799.
  42. Sherman S.B., Sarsour N., Salehi M., Schroering A., Mell B., Joe B., Hill J. W. Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis. Gut Microbes. 2018; 9(5): 400-21. https://dx.doi.org/10.1080/ 19490976.2018.1441664.
  43. Pellock S.J., Redinbo M.R. Glucuronides in the gut: Sugar-driven symbioses between microbe and host. J. Biol. Chem. 2017; 292(21): 8569-76. https://dx.doi. org/10.1074/jbc.R116.767434.
  44. Ahmadi S., Jamilian M., Karamali M., Tajabadi-Ebrahimi M., Jafari P., Taghizadeh M. et al. Probiotic supplementation and the effects on weight loss, glycaemia and lipid profiles in women with polycystic ovary syndrome: a randomized, doubleblind, placebo-controlled trial. Hum. Fertil. (Camb.). 2017; 20(4): 254-61. https://dx.doi.org/10.1080/14647273.2017.1283446.
  45. Shoaei T., Heidari-Beni M., Tehrani H.G., Feizi A., Esmaillzadeh A., Askari G. Effects of probiotic supplementation on pancreatic β-cell function and C-reactive protein in women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial. Int. J. Prev. Med. 2015; 6: 27. https://dx.doi. org/10.4103/2008-7802.153866.
  46. Rashad N.M., Amal S., Amin A.I., Soliman M.H. Effects of probiotics supplementation on macrophage migration inhibitory factor and clinical laboratory feature of polycystic ovary syndrome. J. Funct. Foods. 2017; 36: 317-24. https://dx.doi.org/10.1016/joff.2017.06.029.
  47. Zhang F, Ma T., Cui P., Tamadon A., He S., Huo C. et al. Diversity of the gut microbiota in dihydrotestosterone--induced PCOS rats and the pharmacologic effects of diane-35, probiotics, and berberine. Front. Microbiol. 2019; 10: 175. https://dx.doi.org/10.3389/fmicb.2019.00175.
  48. Forslund K., Hildebrand F., Nielsen T., Falony G., Le Chatelier E., Sunagawa S. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015; 528(7581): 262-6. https://dx.doi.org/10.1038/ nature15766. Erratum in Nature. 2017; 545(7652): 116.
  49. Shin N.R., Lee J.C., Lee H.Y., Kim M.S., Whon T.W., Lee M.S., Bae J.W. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014; 63(5): 727-35. https://dx.doi.org/10.1136/gutjnl-2012-303839.

Supplementary files

Supplementary Files
Action
1. JATS XML

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies