肠道菌群在多囊卵巢综合征中的作用机制

doi:10.12280/gjszjk.20240078

摘要/Abstract

摘要：

肠道微生物群是存在于人体肠道且含量丰富的微生物，通过神经、内分泌等多种途径影响机体生命活动，进而参与许多疾病过程。多囊卵巢综合征（polycystic ovary syndrome，PCOS）是育龄期女性最常见的内分泌疾病之一。肠道菌群可能是PCOS发展的潜在致病因素，其组成改变与胰岛素抵抗、高雄激素血症、慢性炎症和肥胖等临床特征相关。同样，胆汁酸和短链脂肪酸等肠道菌群代谢产物参与PCOS病理过程。在这种情况下，应用粪菌移植、益生菌、益生元和合生元制剂，以及生物碱、黄酮类和多酚等天然产物能够改变肠道菌群组成和代谢产物水平，并且通过调节肠道菌群功能来改善PCOS的内分泌和代谢紊乱。鉴于此，对近几年肠道菌群研究进行综述，以期为临床治疗PCOS提供参考。

关键词: 多囊卵巢综合征, 胃肠道微生物组, 代谢, 治疗

Abstract:

Gastrointestinal microbiome is a rich collection of microorganisms that exist in the human intestine, which affects the life activities of the body via various pathways such as nerve, endocrine, and participates in the process of many diseases. Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. Gastrointestinal microbiome may be a potential pathogenic factor for the development of PCOS, and the change of its composition is correlated with clinical features such as insulin resistance, hyperandrogenism, chronic inflammation and obesity. Similarly, the metabolites of gastrointestinal microbiome such as bile acids and short-chain fatty acids are involved in the pathological process of PCOS. In this context, the agents of fecal microbiota transplantation, probiotics, prebiotics and synbiotics, as well as the natural products including alkaloids, flavonoids and polyphenols, can change the composition of gastrointestinal microbiome and the level of metabolites, and regulate the function of gastrointestinal microbiome to improve the endocrine and metabolic diseases of PCOS. Therefore, the research progress on gastrointestinal microbiome is reviewed in order to provide a reference for clinical therapeutic approaches of PCOS.

Key words: Polycystic ovary syndrome, Gastrointestinal microbiome, Metabolism, Therapy

石百超, 常惠, 王宇, 卢凤娟, 王凯悦, 关木馨, 马良, 吴效科. 肠道菌群在多囊卵巢综合征中的作用机制[J]. 国际生殖健康/计划生育杂志, 2024, 43(3): 238-242.

SHI Bai-chao, CHANG Hui, WANG Yu, LU Feng-juan, WANG Kai-yue, GUAN Mu-xin, MA Liang, WU Xiao-ke. The Role of Gut Microbiota in Patients with Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(3): 238-242.

参考文献 40

[1]	Froment P, Plotton I, Giulivi C, et al. At the crossroads of fertility and metabolism: the importance of AMPK-dependent signaling in female infertility associated with hyperandrogenism[J]. Hum Reprod, 2022, 37(6):1207-1228. doi: 10.1093/humrep/deac067.
[2]	Guo J, Shao J, Yang Y, et al. Gut Microbiota in Patients with Polycystic Ovary Syndrome: a Systematic Review[J]. Reprod Sci, 2022, 29(1):69-83. doi: 10.1007/s43032-020-00430-0. pmid: 33409871
[3]	Thackray VG. Sex, Microbes, and Polycystic Ovary Syndrome[J]. Trends Endocrinol Metab, 2019, 30(1):54-65. doi: 10.1016/j.tem.2018.11.001.
[4]	Corrie L, Awasthi A, Kaur J, et al. Interplay of Gut Microbiota in Polycystic Ovarian Syndrome: Role of Gut Microbiota, Mechanistic Pathways and Potential Treatment Strategies[J]. Pharmaceuticals(Basel), 2023, 16(2):197. doi: 10.3390/ph16020197.
[5]	Zhang H, Butoyi C, Yuan G, et al. Exploring the role of gut microbiota in obesity and PCOS: Current updates and future prospects[J]. Diabetes Res Clin Pract, 2023, 202:110781. doi: 10.1016/j.diabres.2023.110781.
[6]	Dalby MJ. Questioning the foundations of the gut microbiota and obesity[J]. Philos Trans R Soc Lond B Biol Sci, 2023, 378(1888):20220221. doi: 10.1098/rstb.2022.0221.
[7]	贾凡, 郑冬雪, 陈如枫, 等. 不同造模时长对来曲唑诱导的多囊卵巢综合征大鼠肠道菌群的影响[J]. 海南医学院学报, 2022, 28(2):81-91. doi: 10.13210/j.cnki.jhmu.20210823.001.
[8]	Li G, Liu Z, Ren F, et al. Alterations of Gut Microbiome and Fecal Fatty Acids in Patients With Polycystic Ovary Syndrome in Central China[J]. Front Microbiol, 2022, 13:911992. doi: 10.3389/fmicb.2022.911992.
[9]	Liang Y, Ming Q, Liang J, et al. Gut microbiota dysbiosis in polycystic ovary syndrome: association with obesity - a preliminary report[J]. Can J Physiol Pharmacol, 2020, 98(11):803-809. doi: 10.1139/cjpp-2019-0413.
[10]	Amisi CA. Markers of insulin resistance in Polycystic ovary syndrome women: An update[J]. World J Diabetes, 2022, 13(3):129-149. doi: 10.4239/wjd.v13.i3.129. pmid: 35432749
[11]	Mayorga-Ramos A, Barba-Ostria C, Simancas-Racines D, et al. Protective role of butyrate in obesity and diabetes: New insights[J]. Front Nutr, 2022, 9:1067647. doi: 10.3389/fnut.2022.1067647.
[12]	Zhang J, Sun Z, Jiang S, et al. Probiotic Bifidobacterium lactis V9 Regulates the Secretion of Sex Hormones in Polycystic Ovary Syndrome Patients through the Gut-Brain Axis[J]. mSystems, 2019, 4(2):e00017-19. doi: 10.1128/mSystems.00017-19.
[13]	王晶, 戴若冰, 葛含婷, 等. 多囊卵巢综合征与肠道菌群失调中西医结合研究进展[J]. 中国中西医结合杂志, 2024, 44(1):120-126. doi: 10.7661/j.cjim.20230608.276.
[14]	Gao A, Su J, Liu R, et al. Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome[J]. Nat Commun, 2021, 12(1):7080. doi: 10.1038/s41467-021-27187-7. pmid: 34873153
[15]	Prabhu YD, Borthakur A, A G S, et al. Increased pro-inflammatory cytokines in ovary and effect of γ-linolenic acid on adipose tissue inflammation in a polycystic ovary syndrome model[J]. J Reprod Immunol, 2021, 146:103345. doi: 10.1016/j.jri.2021.103345.
[16]	Burrichter AG, Dörr S, Bergmann P, et al. Bacterial microcompartments for isethionate desulfonation in the taurine-degrading human-gut bacterium Bilophila wadsworthia[J]. BMC Microbiol, 2021, 21(1):340. doi: 10.1186/s12866-021-02386-w. pmid: 34903181
[17]	Cifarelli V, Peche VS, Abumrad NA. Vascular and lymphatic regulation of gastrointestinal function and disease risk[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2022, 1867(11):159207. doi: 10.1016/j.bbalip.2022.159207.
[18]	周颖, 高天. 肠道菌群粪便移植与多囊卵巢综合征发病关系研究[J]. 中国妇产科临床杂志, 2021, 22(4):438-440. doi: 10.13390/j.issn.1672-1861.2021.04.035.
[19]	安洁, 周琴, 曹珍珍, 等. 多囊卵巢综合征患者与健康人群肠道菌群差异性分析[J]. 中国微生态学杂志, 2021, 33(7):825-831. doi: 10.13381/j.cnki.cjm.202107017.
[20]	Wang L, Zhou J, Gober HJ, et al. Alterations in the intestinal microbiome associated with PCOS affect the clinical phenotype[J]. Biomed Pharmacother, 2021, 133:110958. doi: 10.1016/j.biopha.2020.110958. pmid: 33171400
[21]	Zhang M, Hu R, Huang Y, et al. Present and Future: Crosstalks Between Polycystic Ovary Syndrome and Gut Metabolites Relating to Gut Microbiota[J]. Front Endocrinol(Lausanne), 2022, 13:933110. doi: 10.3389/fendo.2022.933110.
[22]	唐银佩, 朱正望, 王兵, 等. 中医药调控肠道菌群治疗代谢相关脂肪性肝病的机制[J]. 中国实验方剂学杂志,2024-02-23. doi:10.13422/j.cnki.syfjx.20240826.
[23]	Qi X, Yun C, Sun L, et al. Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome[J]. Nat Med, 2019, 25(8):1225-1233. doi: 10.1038/s41591-019-0509-0. pmid: 31332392
[24]	Wang K, Zhou M, Si H, et al. Gut microbiota-mediated IL-22 alleviates metabolic inflammation[J]. Life Sci, 2023, 334:122229. doi: 10.1016/j.lfs.2023.122229.
[25]	Hamamah S, Gheorghita R, Lobiuc A, et al. Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols[J]. Front Med(Lausanne), 2022, 9:1060581. doi: 10.3389/fmed.2022.1060581.
[26]	Corrie L, Gulati M, Vishwas S, et al. Combination therapy of curcumin and fecal microbiota transplant: Potential treatment of polycystic ovarian syndrome[J]. Med Hypotheses, 2021, 154:110644. doi: 10.1016/j.mehy.2021.110644.
[27]	Martinelli S, Nannini G, Cianchi F, et al. Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments[J]. Microorganisms, 2023, 11(10):2407. doi: 10.3390/microorganisms11102407.
[28]	Corrie L, Gulati M, Awasthi A, et al. Harnessing the dual role of polysaccharides in treating gastrointestinal diseases: As therapeutics and polymers for drug delivery[J]. Chem Biol Interact, 2022, 368:110238. doi: 10.1016/j.cbi.2022.110238.
[29]	Miao C, Guo Q, Fang X, et al. Effects of probiotic and synbiotic supplementation on insulin resistance in women with polycystic ovary syndrome: a meta-analysis[J]. J Int Med Res, 2021, 49(7):3000605211031758. doi: 10.1177/03000605211031758.
[30]	Li T, Zhang Y, Song J, et al. Yogurt Enriched with Inulin Ameliorated Reproductive Functions and Regulated Gut Microbiota in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Mice[J]. Nutrients, 2022, 14(2):279. doi: 10.3390/nu14020279.
[31]	Yde CC, Jensen HM, Christensen N, et al. Polydextrose with and without Bifidobacterium animalis ssp. lactis 420 drives the prevalence of Akkermansia and improves liver health in a multi-compartmental obesogenic mice study[J]. PLoS One, 2021, 16(12):e0260765. doi: 10.1371/journal.pone.0260765.
[32]	Abookleesh FL, Al-Anzi BS, Ullah A. Potential Antiviral Action of Alkaloids[J]. Molecules, 2022, 27(3):903. doi: 10.3390/molecules27030903.
[33]	Cheng H, Liu J, Tan Y, et al. Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine[J]. J Pharm Anal, 2022, 12(4):541-555. doi: 10.1016/j.jpha.2021.10.003. pmid: 36105164
[34]	孟欢, 侯晓婷, 张华敏, 等. 中药天然产物治疗炎症性肠病的研究进展[J]. 中草药, 2023, 54(10):3349-3369. doi: 10.7501/j.issn.0253-2670.2023.10.032.
[35]	Shabbir U, Rubab M, Daliri EB, et al. Curcumin, Quercetin, Catechins and Metabolic Diseases: The Role of Gut Microbiota[J]. Nutrients, 2021, 13(1):206. doi: 10.3390/nu13010206.
[36]	Huang L, Zheng T, Hui H, et al. Soybean isoflavones modulate gut microbiota to benefit the health weight and metabolism[J]. Front Cell Infect Microbiol, 2022, 12:1004765. doi: 10.3389/fcimb.2022.1004765.
[37]	Wu YX, Yang XY, Han BS, et al. Naringenin regulates gut microbiota and SIRT1/ PGC-1α signaling pathway in rats with letrozole-induced polycystic ovary syndrome[J]. Biomed Pharmacother, 2022, 153:113286. doi: 10.1016/j.biopha.2022.113286.
[38]	Corrie L, Kaur J, Awasthi A, et al. Multivariate Data Analysis and Central Composite Design-Oriented Optimization of Solid Carriers for Formulation of Curcumin-Loaded Solid SNEDDS: Dissolution and Bioavailability Assessment[J]. Pharmaceutics, 2022, 14(11):2395. doi: 10.3390/pharmaceutics14112395.
[39]	Lippolis T, Cofano M, Caponio GR, et al. Bioaccessibility and Bioavailability of Diet Polyphenols and Their Modulation of Gut Microbiota[J]. Int J Mol Sci, 2023, 24(4):3813. doi: 10.3390/ijms24043813.
[40]	Islam T, Albracht-Schulte K, Ramalingam L, et al. Anti-inflammatory mechanisms of polyphenols in adipose tissue: role of gut microbiota, intestinal barrier integrity and zinc homeostasis[J]. J Nutr Biochem, 2023, 115:109242. doi: 10.1016/j.jnutbio.2022.109242.