Microbiome and PCOS: State-of-Art and Future Aspects
Abstract
:1. Introduction
2. Materials and Methods
3. Gut Microbiome and PCOS
3.1. Gut Microbiome Changes in Women with PCOS
3.2. Gut Microbiome and Insulin-Resistance
3.3. Gut Microbiome and Sexual Hormones
3.4. Pathway Leading to PCOS
4. Lower Genital Tract Microbiome in PCOS Patients
5. Diet and Medication: How to Change Gut Microbiome
6. Therapeutic Opportunities
6.1. Probiotic, Prebiotics and Synbiotics
6.2. Fecal Microbiota Transplantation
6.3. New Therapeutic Options (IL-22)
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
PCOS | polycystic vary syndrome |
HA | hyperandrogenism |
NIH | National Institutes of Health |
ESHRE/ASRM | European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine |
PCOM | polycystic ovarian morphology |
DOGMA | dysbiosis of gut microbiota |
LPS | lipopolysaccharide |
MeSH | medical subject headings |
IR | insulin resistance |
BMI | body mass index |
PYY | peptide YY |
GDCA | glycodeoxycholic acid |
TUDCA | tauroursodeoxycholic acid |
SCFA | short-chain fatty acids |
LGT | lower genital tract |
BV | bacterial vaginosis |
AUC | area under the curve |
WHO | World Health Organization |
TG | triglycerides |
VLDL | very-low-density lipoprotein |
HOMA-IR | Homeostatic Model Assessment of Insulin Resistance |
FAI | Free Androgen Index |
MDA | malondialdehyde |
SHBG | sex hormone binding globulin |
NO | nitric oxide |
FOS | fructooligosaccharides |
GOS | galactooligosaccharides |
FMT | fecal microbiota transplantation |
References
- Teede, H.J.; Misso, M.L.; Costello, M.F.; Dokras, A.; Laven, J.; Moran, L.; Piltonen, T.; Norman, R.J.; Andersen, M.; Azziz, R.; et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum. Reprod. 2018, 33, 1602–1618. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bozdag, G.; Mumusoglu, S.; Zengin, D.; Karabulut, E.; Yildiz, B.O. The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis. Hum. Reprod. 2016, 31, 2841–2855. [Google Scholar] [CrossRef]
- Lambrinoudaki, I.; Armeni, E. Cardiovascular Risk in Postmenopausal Women with Polycystic Ovary Syndrome. Curr. Vasc. Pharmacol. 2019, 17, 579–590. [Google Scholar] [CrossRef] [PubMed]
- Puurunen, J.; Piltonen, T.; Morin-Papunen, L.; Perheentupa, A.; Järvelä, I.; Ruokonen, A.; Tapanainen, J.S. Unfavorable Hormonal, Metabolic, and Inflammatory Alterations Persist after Menopause in Women with PCOS. J. Clin. Endocrinol. Metab. 2011, 96, 1827–1834. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Della Corte, L.; La Rosa, V.L.; Rapisarda, A.M.C.; Valenti, G.; Morra, I.; Boccellino, A.; Zizolfi, B.; Santangelo, F.; De Rosa, N.; Sapia, F.; et al. Current evidences and future perspectives on patient-oriented treatments for polycystic ovary syn-drome: An overview. Ital. J. Gynaecol. Obstet. 2018, 30, 2385. [Google Scholar]
- Azziz, R.; Carmina, E.; Chen, Z.; Dunaif, A.; Laven, J.S.E.; Legro, R.S.; Lizneva, D.; Horowtiz-Natterson, B.; Teede, H.J.; Yildiz, B.O. Polycystic ovary syndrome. Nat. Rev. Dis. Primers 2016, 2, 16057. [Google Scholar] [CrossRef]
- Zawadzki, J.K.; Dunaif, A. Diagnostic criteria for polycystic ovary syndrome: Toward a rational approach. In Polycystic Ovary Syndrome; Dunaif, A., Givens, J.R., Haseltine, F., Merriam, G.R., Eds.; Blackwell Scientific Publications: Oxford, UK, 1992; pp. 377–384. [Google Scholar]
- Chang, J.; Azziz, R.; Legro, R.; Dewailly, D.; Franks, S.; Tarlatzis, R.; Fauser, B.; Balen, A.; Bouchard, P.; Dalgien, E.; et al. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril. 2004, 81, 19–25. [Google Scholar] [CrossRef]
- Giampaolino, P.; Della Corte, L.; De Rosa, N.; Mercorio, A.; Bruzzese, D.; Bifulco, G. Ovarian volume and PCOS: A controversial issue. Gynecol. Endocrinol. 2017, 34, 229–232. [Google Scholar] [CrossRef]
- Giampaolino, P.; Morra, I.; Della Corte, L.; Sparice, S.; Di Carlo, C.; Nappi, C.; Bifulco, G. Serum anti-Mullerian hormone levels after ovarian drilling for the second-line treatment of polycystic ovary syndrome: A pilot-randomized study comparing laparoscopy and transvaginal hydrolaparoscopy. Gynecol. Endocrinol. 2017, 33, 26–29. [Google Scholar] [CrossRef] [Green Version]
- Giampaolino, P.; De Rosa, N.; Della Corte, L.; Morra, I.; Mercorio, A.; Nappi, C.; Bifulco, G. Operative transvaginal hydrolaparoscopy improve ovulation rate after clomiphene failure in polycystic ovary syndrome. Gynecol. Endocrinol. 2017, 34, 32–35. [Google Scholar] [CrossRef]
- Franks, S.; I McCarthy, M.; Hardy, K. Development of polycystic ovary syndrome: Involvement of genetic and environmental factors. Int. J. Androl. 2006, 29, 278–285. [Google Scholar] [CrossRef]
- Li, Y.; Chen, C.; Ma, Y.; Xiao, J.; Luo, G.; Li, Y.; Wu, D. Multi-system reproductive metabolic disorder: Significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS). Life Sci. 2019, 228, 167–175. [Google Scholar] [CrossRef]
- Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; et al. Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes 2007, 56, 1761–1772. [Google Scholar] [CrossRef] [Green Version]
- Turnbaugh, P.J.; Ley, R.E.; Mahowald, M.A.; Magrini, V.; Mardis, E.R.; Gordon, J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nat. Cell Biol. 2006, 444, 1027–1031. [Google Scholar] [CrossRef]
- Dabke, K.; Hendrick, G.; Devkota, S. The gut microbiome and metabolic syndrome. J. Clin. Investig. 2019, 129, 4050–4057. [Google Scholar] [CrossRef]
- Tremellen, K.; Pearce, K. Dysbiosis of Gut Microbiota (DOGMA)—A novel theory for the development of Polycystic Ovarian Syndrome. Med. Hypotheses 2012, 79, 104–112. [Google Scholar] [CrossRef] [PubMed]
- Hong, X.; Qin, P.; Huang, K.; Ding, X.; Ma, J.; Xuan, Y.; Zhu, X.; Peng, D.; Wang, B. Association between polycystic ovary syndrome and the vaginal microbiome: A case-control study. Clin. Endocrinol. 2020, 93, 52–60. [Google Scholar] [CrossRef] [PubMed]
- Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K.S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T.; et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010, 464, 59–65. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gill, S.R.; Pop, M.; DeBoy, R.T.; Eckburg, P.B.; Turnbaugh, P.J.; Samuel, B.S.; Gordon, J.I.; Relman, D.A.; Fraser-Liggett, C.M.; Nelson, K.E. Metagenomic Analysis of the Human Distal Gut Microbiome. Science 2006, 312, 1355–1359. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Clemente, J.C.; Ursell, L.K.; Parfrey, L.W.; Knight, R. The Impact of the Gut Microbiota on Human Health: An Integrative View. Cell 2012, 148, 1258–1270. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eckburg, P.B.; Bik, E.M.; Bernstein, C.N.; Purdom, E.; Dethlefsen, L.; Sargent, M.; Gill, S.R.; Nelson, K.E.; Relman, D.A. Diversity of the Human Intestinal Microbial Flora. Science 2005, 308, 1635–1638. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lindheim, L.; Bashir, M.; Münzker, J.; Trummer, C.; Zachhuber, V.; Leber, B.; Horvath, A.; Pieber, T.R.; Gorkiewicz, G.; Stadlbauer, V.; 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, e0168390. [Google Scholar] [CrossRef]
- Liu, R.; Zhang, C.; Shi, Y.; Zhang, F.; Li, L.; Wang, X.; Ling, Y.; Fu, H.; Dong, W.; Shen, J.; et al. Dysbiosis of Gut Microbiota Associated with Clinical Parameters in Polycystic Ovary Syndrome. Front. Microbiol. 2017, 8, 324. [Google Scholar] [CrossRef] [PubMed]
- 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 Hyperandrogenism. J. Clin. Endocrinol. Metab. 2018, 103, 1502–1511. [Google Scholar] [CrossRef] [PubMed]
- Insenser, M.; Murri, M.; Del Campo, R.; Ángeles Martínez-García, M.; Fernández-Durán, 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, 2552–2562. [Google Scholar] [CrossRef] [PubMed]
- Thursby, E.; Juge, N. Introduction to the human gut microbiota. Biochem. J. 2017, 474, 1823–1836. [Google Scholar] [CrossRef] [PubMed]
- Thackray, V.G. Sex, Microbes, and Polycystic Ovary Syndrome. Trends Endocrinol. Metab. 2019, 30, 54–65. [Google Scholar] [CrossRef] [PubMed]
- Fangyuan, C.; Zhiwen, L.A.I.; Zusen, X.U. Analysis of the gut microbial composition in polycystic ovary syndrome with acne. Zigong Matern. Child. Health Hosp. 2019, 35, 2246–2251. [Google Scholar]
- Zhou, L.; Ni, Z.; Cheng, W.; Yu, J.; Sun, S.; Zhai, D.; Yu, C.; Cai, Z. Characteristic gut microbiota and predicted metabolic functions in women with PCOS. Endocr. Connect. 2020, 9, 63–73. [Google Scholar] [CrossRef]
- Qi, X.; Yun, C.; Sun, L.; Xia, J.; Wu, Q.; Wang, L.; Wang, L.; Zhang, Y.; Liang, X.; Gonzalez, F.J.; et al. Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome. Nat. Med. 2019, 25, 1225–1233. [Google Scholar] [CrossRef]
- Ley, R.E. Gut microbiota in 2015: Prevotella in the gut: Choose carefully. Nat. Rev. Gastroenterol. Hepatol. 2016. [Google Scholar] [CrossRef]
- Lukens, J.R.; Gurung, P.; Vogel, P.; Johnson, G.R.; Carter, R.A.; McGoldrick, D.J.; Bandi, S.R.; Calabrese, C.R.; Vande Walle, L.; Lamkanfi, M.; et al. Dietary modulation of the microbiome affects autoinflammatory disease. Nature 2014, 516, 246e9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zeng, B.; Lai, Z.; Sun, L.; Zhang, Z.; Yang, J.; Li, Z.; Lin, J.; Zhang, Z. Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): A pilot study. Res. Microbiol. 2019, 170, 43–52. [Google Scholar] [CrossRef] [PubMed]
- Sherman, S.; Sarsour, N.; Salehi, M.; Schroering, A.; Mell, B.; Joe, B.; Hill, J.W. Prenatal androgen ex-posure causes hypertension and gut microbiota dysbiosis. Gut Microbes. 2018, 9, 400–421. [Google Scholar] [CrossRef] [PubMed]
- 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, e0153196. [Google Scholar] [CrossRef] [Green Version]
- Jiao, N.; Baker, S.S.; Nugent, C.A.; Tsompana, M.; Cai, L.; Wang, Y.; Buck, M.J.; Genco, R.J.; Baker, R.D.; Zhu, R.; et al. Gut microbiome may con-tribute to insulin resistance and systemic inflammation in obese rodents: A meta-analysis. Physiol Genomics. 2018, 50, 54–244. [Google Scholar] [CrossRef] [Green Version]
- Scheithauer, T.P.M.; Dallinga-Thie, G.M.; De Vos, W.M.; Nieuwdorp, M.; Van Raalte, D.H. Causality of small and large intestinal microbiota in weight regulation and insulin resistance. Mol. Metab. 2016, 5, 759–770. [Google Scholar] [CrossRef] [PubMed]
- Bäckhed, F.; Ding, H.; Wang, T.; Hooper, L.V.; Koh, G.Y.; Nagy, A.; Semenkovich, C.F.; Gordon, J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 2004, 101, 15718–15723. [Google Scholar] [CrossRef] [Green Version]
- Vrieze, A.; Van Nood, E.; Holleman, F.; Salojärvi, J.; Kootte, R.S.; Bartelsman, J.F.W.M.; Dallinga–Thie, G.M.; Ackermans, M.T.; Serlie, M.J.; Oozeer, R.; et al. Transfer of Intestinal Microbiota from Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome. Gastroenterology 2012, 143, 913–916. [Google Scholar] [CrossRef] [PubMed]
- He, F.-F.; Li, Y.-M. Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: A review. J. Ovarian Res. 2020, 13, 1–13. [Google Scholar] [CrossRef]
- Andreasen, A.S.; Larsen, N.; Pedersen-Skovsgaard, T.; Berg, R.M.G.; Møller, K.; Svendsen, K.D.; Jakobsen, M.; Pedersen, B.K. Effects ofLactobacillus acidophilusNCFM on insulin sensitivity and the systemic inflammatory response in human subjects. Br. J. Nutr. 2010, 104, 1831–1838. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lang, U.E.; Beglinger, C.; Schweinfurth, N.; Walter, M.H.; Borgwardt, S. Nutritional Aspects of Depression. Cell. Physiol. Biochem. 2015, 37, 1029–1043. [Google Scholar] [CrossRef]
- Lin, T.; Li, S.; Xu, H.; Zhou, H.; Feng, R.; Liu, W.; Sun, Y.; Ma, J. Gastrointestinal hormone secretion in women with polycystic ovary syndrome: An observational study. Hum. Reprod. 2015, 30, 2639–2644. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Houjeghani, S.; Gargari, B.P.; Farzadi, L. Serum Leptin and Ghrelin Levels in Women with Polycystic Ovary Syndrome: Correlation with Anthropometric, Metabolic, and Endocrine Parameters. Int. J. Fertil Steril 2012, 6, 117–126. [Google Scholar] [PubMed]
- Arusoglu, G.; Koksal, G.; Cinar, N.; Tapan, S.; Aksoy, D.Y.; Yildiz, B.O. Basal and Meal-Stimulated Ghrelin, PYY, CCK Levels and Satiety in Lean Women With Polycystic Ovary Syndrome: Effect of Low-Dose Oral Contraceptive. J. Clin. Endocrinol. Metab. 2013, 98, 4475–4482. [Google Scholar] [CrossRef] [Green Version]
- Falony, G.; Joossens, M.; Vieira-Silva, S.; Wang, J.; Darzi, Y.; Faust, K.; Kurilshikov, A.; Bonder, M.J.; Valles-Colomer, M.; Vandeputte, D.; et al. Population-level analysis of gut microbiome variation. Science 2016, 352, 560–564. [Google Scholar] [CrossRef]
- Dominianni, C.; Sinha, R.; Goedert, J.J.; Pei, Z.; Yang, L.; Hayes, R.B.; Ahn, J. Sex, Body Mass Index, and Dietary Fiber Intake Influence the Human Gut Microbiome. PLoS ONE 2015, 10, e0124599. [Google Scholar] [CrossRef] [Green Version]
- Chen, T.; Long, W.; Zhang, C.; Liu, S.; Zhao, L.; Hamaker, B.R. Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota. Sci. Rep. 2017, 7, 1–7. [Google Scholar] [CrossRef]
- Haro, C.; Rangel-Zúñiga, O.A.; Alcalá-Díaz, J.F.; Gómez-Delgado, F.; Pérez-Martínez, P.; Delgado-Lista, J.; Quintana-Navarro, G.M.; Landa, B.B.; Cortés, J.A.N.; Tena-Sempere, M.; et al. Intestinal Microbiota Is Influenced by Gender and Body Mass Index. PLoS ONE 2016, 11, e0154090. [Google Scholar] [CrossRef] [Green Version]
- Harada, N.; Hanaoka, R.; Horiuchi, H.; Kitakaze, T.; Mitani, T.; Inui, H.; Yamaji, R. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice. Sci. Rep. 2016, 6, 23001. [Google Scholar] [CrossRef]
- Choi, S.; Hwang, Y.-J.; Shin, M.-J.; Yi, H. Difference in the Gut Microbiome between Ovariectomy-Induced Obesity and Diet-Induced Obesity. J. Microbiol. Biotechnol. 2017, 27, 2228–2236. [Google Scholar] [CrossRef]
- Barrea, L.; Marzullo, P.; Muscogiuri, G.; Di Somma, C.; Scacchi, M.; Orio, F.; Aimaretti, G.; Colao, A.; Savastano, S. Source and amount of carbohydrate in the diet and inflammation in women with polycystic ovary syndrome. Nutr. Res. Rev. 2018, 31, 291–301. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Zhou, J.; Gober, H.-J.; Leung, W.T.; Huang, Z.; Pan, X.; Li, C.; Zhang, N.; Wang, L. Alterations in the intestinal microbiome associated with PCOS affect the clinical phenotype. Biomed. Pharmacother. 2021, 133, 110958. [Google Scholar] [CrossRef]
- Ratajczak, W.; Rył, A.; Mizerski, A.; Walczakiewicz, K.; Sipak, O.; Laszczyńska, M. Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs). Acta Biochim. Pol. 2019, 66, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, J.; Sun, Z.; Jiang, S.; Bai, X.; Ma, C.; Peng, Q.; Chen, K.; Chang, H.; Fang, T.; Zhang, H. Probiotic Bifidobacterium lactis V9 Regulates the Secretion of Sex Hormones in Polycystic Ovary Syndrome Patients through the Gut-Brain Axis. mSystems 2019, 4, e00017-19. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kumar, P.S. Sex and the subgingival microbiome: Do female sex steroids affect periodontal bacteria? Periodontol. 2000 2013, 61, 103–124. [Google Scholar] [CrossRef] [PubMed]
- Muhleisen, A.L.; Herbst-Kralovetz, M.M. Menopause and the vaginal microbiome. Maturitas 2016, 91, 42–50. [Google Scholar] [CrossRef]
- Stumpf, R.M.; Wilson, B.A.; Rivera, A.; Yildirim, S.; Yeoman, C.J.; Polk, J.D.; White, B.A.; Leigh, S.R. The primate vaginal microbiome: Comparative context and implications for human health and disease. Am. J. Phys. Anthr. 2013, 152, 119–134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gajer, P.; Brotman, R.M.; Bai, G.; Sakamoto, J.; Schütte, U.M.E.; Zhong, X.; Koenig, S.S.K.; Fu, L.; Ma, Z.S.; Zhou, X.; et al. Temporal Dynamics of the Human Vaginal Microbiota. Sci. Transl. Med. 2012, 4, 132ra52. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, C.; Song, X.; Chunwei, Z.; Zhong, H.; Dai, J.; Lan, Z.; Li, F.; Yu, X.; Feng, Q.; Wang, Z.; et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun. 2017, 8, 1–11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Anahtar, M.N.; Gootenberg, D.B.; Mitchell, C.M.; Kwon, D.S. Cervicovaginal Microbiota and Reproductive Health: The Virtue of Simplicity. Cell Host Microbe 2018, 23, 159–168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tu, Y.; Zheng, G.; Ding, G.; Wu, Y.; Xi, J.; Ge, Y.; Gu, H.; Wang, Y.; Sheng, J.; Liu, X.; et al. Comparative Analysis of Lower Genital Tract Microbiome Between PCOS and Healthy Women. Front. Physiol. 2020, 11. [Google Scholar] [CrossRef]
- Gupta, S.; Kakkar, V.; Bhushan, I. Crosstalk between Vaginal Microbiome and Female Health: A review. Microb. Pathog. 2019, 136, 103696. [Google Scholar] [CrossRef]
- Al-Memar, M.; Bobdiwala, S.; Fourie, H.; Mannino, R.; Lee, Y.S.; Smith, A.; Marchesi, J.R.; Timmerman, D.; Bourne, T.; Bennett, P.R.; et al. The association between vaginal bacterial composition and miscarriage: A nested case–control study. BJOG Int. J. Obstet. Gynaecol. 2020, 127, 264–274. [Google Scholar] [CrossRef] [Green Version]
- Peelen, M.J.; Luef, B.M.; Lamont, R.F.; De Milliano, I.; Jensen, J.S.; Limpens, J.; Hajenius, P.J.; Jørgensen, J.S.; Menon, R. The influence of the vaginal microbiota on preterm birth: A systematic review and recommendations for a minimum dataset for future research. Placenta 2019, 79, 30–39. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koedooder, R.; Singer, M.; Schoenmakers, S.; Savelkoul, P.H.M.; A Morré, S.; De Jonge, J.D.; Poort, L.; Cuypers, W.J.S.S.; Beckers, N.G.M.; Broekmans, F.J.M.; et al. The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: A prospective study. Hum. Reprod. 2019, 34, 1042–1054. [Google Scholar] [CrossRef] [PubMed]
- Coudray, M.S.; Madhivanan, P. Bacterial vaginosis—A brief synopsis of the literature. Eur. J. Obstet. Gynecol. Reprod. Biol. 2020, 245, 143–148. [Google Scholar] [CrossRef]
- Vestby, L.K.; Grønseth, T.; Simm, R.; Nesse, L.L. Bacterial Biofilm and its Role in the Pathogenesis of Disease. Antibiotics 2020, 9, 59. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Onderdonk, A.B.; Delaney, M.L.; Fichorova, R.N. The Human Microbiome during Bacterial Vaginosis. Clin. Microbiol. Rev. 2016, 29, 223–238. [Google Scholar] [CrossRef] [Green Version]
- Singh, R.K.; Chang, H.-W.; Yan, D.; Lee, K.M.; Ucmak, D.; Wong, K.; Abrouk, M.; Farahnik, B.; Nakamura, M.; Zhu, T.H.; et al. Influence of diet on the gut microbiome and implications for human health. J. Transl. Med. 2017, 15, 1–17. [Google Scholar] [CrossRef] [Green Version]
- Gentile, C.L.; Weir, T.L. The gut microbiota at the intersection of diet and human health. Science 2018, 362, 776–780. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klement, R.J.; Pazienza, V. Impact of Different Types of Diet on Gut Microbiota Profiles and Cancer Prevention and Treatment. Medicina 2019, 55, 84. [Google Scholar] [CrossRef] [Green Version]
- Xue, J.; Li, X.; Liu, P.; Li, K.; Sha, L.; Yang, X.; Zhu, L.; Wang, Z.; Dong, Y.; Zhang, L.; et al. Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice. Endocr. J. 2019, 66, 859–870. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karamali, M.; Eghbalpour, S.; Rajabi, S.; Jamilian, M.; Bahmani, F.; Tajabadi-Ebrahimi, M.; Keneshlou, F.; Mirhashemi, S.M.; Chamani, M.; Hashem Gelougerdi, S.; et al. Effects of Probiotic Supplementation on Hormonal Profiles, Biomarkers of Inflammation and Oxida-tive Stress in Women With Polycystic Ovary Syndrome: A Randomized, Double-Blind, Pla-cebo-Controlled Trial. Arch. Iran Med. 2018, 21, 1–7. [Google Scholar] [PubMed]
- Zhao, X.; Jiang, Y.; Xi, H.; Chen, L.; Feng, X. Exploration of the Relationship Between Gut Microbiota and Polycystic Ovary Syndrome (PCOS): A Review. Geburtshilfe Frauenheilkd. 2020, 80, 161–171. [Google Scholar] [CrossRef] [Green Version]
- Della Corte, L.; Foreste, V.; Barra, F.; Gustavino, C.; Alessandri, F.; Centurioni, M.G.; Ferrero, S.; Bifulco, G.; Giampaolino, P. Current and experimental drug therapy for the treatment of polycystic ovarian syndrome. Expert Opin. Investig. Drugs 2020, 29, 819–830. [Google Scholar] [CrossRef]
- Guarner, F.; Khan, A.G.; Garisch, J.; Eliakim, R.; Gangl, A.; Thomson, A.; Krabshuis, J.; Lemair, T.; Kaufmann, P.; De Paula, J.A.; et al. World Gastroenterology Organisation Global Guidelines. J. Clin. Gastroenterol. 2012, 46, 468–481. [Google Scholar] [CrossRef]
- Ahmadi, S.; Jamilian, M.; Karamali, M.; Tajabadi-Ebrahimi, M.; Jafari, P.; Taghizadeh, M.; Memarzadeh, M.R.; Asemi, Z. Probiotic supplementation and the effects on weight loss, glycaemia and lipid profiles in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Hum. Fertil. 2017, 20, 254–261. [Google Scholar] [CrossRef]
- Askari, G.; Shoaei, T.; Tehrani, H.G.; Heidari-Beni, M.; Feizi, A.; Esmaillzadeh, A. 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. [Google Scholar] [CrossRef]
- Rashad, N.M.; El-Shal, A.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, 317–324. [Google Scholar] [CrossRef]
- Heshmati, J.; Farsi, F.; Yosaee, S.; Razavi, M.; Rezaeinejad, M.; Karimie, E.; Sepidarkish, M. The Effects of Probiotics or Synbiotics Supplementation in Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Probiotics Antimicrob. Proteins 2019, 11, 1236–1247. [Google Scholar] [CrossRef]
- Shamasbi, S.G.; Ghanbari-Homayi, S.; Mirghafourvand, M. The effect of probiotics, prebiotics, and synbiotics on hormonal and inflammatory indices in women with polycystic ovary syndrome: A systematic review and meta-analysis. Eur. J. Nutr. 2019, 59, 433–450. [Google Scholar] [CrossRef] [PubMed]
- Shamasbi, S.G.; Dehgan, P.; Charandabi, S.M.-A.; Aliasgarzadeh, A.; Mirghafourvand, M. The effect of resistant dextrin as a prebiotic on metabolic parameters and androgen level in women with polycystic ovarian syndrome: A randomized, triple-blind, controlled, clinical trial. Eur. J. Nutr. 2018, 58, 629–640. [Google Scholar] [CrossRef] [PubMed]
- Yurtdaş, G.; Akdevelioğlu, Y. A New Approach to Polycystic Ovary Syndrome: The Gut Microbiota. J. Am. Coll. Nutr. 2019, 39, 371–382. [Google Scholar] [CrossRef]
- Ghanei, N.; Rezaei, N.; Amiri, G.A.; Zayeri, F.; Makki, G.; Nasseri, E. The probiotic supplementation reduced inflammation in polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. J. Funct. Foods 2018, 42, 306–311. [Google Scholar] [CrossRef]
- Altun, H.K.; Yıldız, E.A. Prebiyotikler ve Probiyotiklerin Diyabet ile Iliskisi. Turk. J. Life Sci. 2017, 11, 63–70. [Google Scholar]
- Fernandes, R.; Rosario, V.A.D.; Mocellin, M.C.; Kuntz, M.G.; Trindade, E.B. Effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adult patients with overweight or obesity: A systematic review. Clin. Nutr. 2017, 36, 1197–1206. [Google Scholar] [CrossRef] [PubMed]
- Moore, T.; Rodriguez, A.; Bakken, J.S. Fecal Microbiota Transplantation: A Practical Update for the Infectious Disease Specialist. Clin. Infect. Dis. 2014, 58, 541–545. [Google Scholar] [CrossRef]
- Qi, X.; Yun, C.; Liao, B.; Qiao, J.; Pang, Y. The therapeutic effect of interleukin-22 in high androgen-induced polycystic ovary syndrome. J. Endocrinol. 2020, 245, 281–289. [Google Scholar] [CrossRef] [PubMed]
- Kriebs, A. IL-22 links gut microbiota to PCOS. Nat. Rev. Endocrinol. 2019, 15, 565. [Google Scholar] [CrossRef]
PCOS | |
---|---|
Microorganisms | Effect |
Increase of Escherichia and Shigella | Altered production of short-chain fatty acids |
Increase of Bacteroides vulgatus | Reduction in the levels of glycodeoxycholic and tauroursodeoxycholic acid |
Decrease of Prevotellaceae | Loss of production of anti-inflammatory metabolites |
Decrease of Lactobacilli and Bifidobacteria | Reduced immunity and nutrient absorption |
Insuline Resistance (IR) | |
---|---|
Microorganisms | Effect |
Imbalance of gut microbiota (significant difference in the abundance of Ruminococcaceae and Lachnospiraceae) | Increased intestinal permeability → chronic low-grade inflammation by activating the immune system → production of proinflammatory cytokines interfere with insulin receptor function → IR/hyperinsulinemia |
Increase of Bacteroides species | Altered secretion of Ghrelin and peptide YY → IR/hyperinsulinemia. |
Therapy | Studied Model | Effects | Reference |
---|---|---|---|
Probiotic | Human | Positive effect on glycemic control, with lower insulin levels, and on lipid metabolism, by increasing HDL and lowering TG serum levels; positive control of hormonal and inflammatory indicators | [76,77,78,79,80,81] |
Prebiotics | Human | Positive effects on metabolic markers and immunomodulatory properties; considerable decrease in fasting plasma glucose, serum TG, total cholesterol, and LDL cholesterol, and significant increase in HDL cholesterol levels. | [75,82,83] |
FMT | Mice | Metabolic improvements in FMT-treated PCOS rats vs. the untreated group, with decreased androgen levels, estradiol and estrone increase and normalization of ovarian function. | [36] |
IL-22 | Mice | Improved insulin-resistance, estrous cycle and ovary morphology. | [84,85] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Giampaolino, P.; Foreste, V.; Di Filippo, C.; Gallo, A.; Mercorio, A.; Serafino, P.; Improda, F.P.; Verrazzo, P.; Zara, G.; Buonfantino, C.; et al. Microbiome and PCOS: State-of-Art and Future Aspects. Int. J. Mol. Sci. 2021, 22, 2048. https://doi.org/10.3390/ijms22042048
Giampaolino P, Foreste V, Di Filippo C, Gallo A, Mercorio A, Serafino P, Improda FP, Verrazzo P, Zara G, Buonfantino C, et al. Microbiome and PCOS: State-of-Art and Future Aspects. International Journal of Molecular Sciences. 2021; 22(4):2048. https://doi.org/10.3390/ijms22042048
Chicago/Turabian StyleGiampaolino, Pierluigi, Virginia Foreste, Claudia Di Filippo, Alessandra Gallo, Antonio Mercorio, Paolo Serafino, Francesco Paolo Improda, Paolo Verrazzo, Giuseppe Zara, Cira Buonfantino, and et al. 2021. "Microbiome and PCOS: State-of-Art and Future Aspects" International Journal of Molecular Sciences 22, no. 4: 2048. https://doi.org/10.3390/ijms22042048