肠道菌群及肠道代谢物与多囊卵巢综合征的关系

doi:10.12280/gjszjk.20230383

摘要/Abstract

摘要：

人体肠道微生物丰富多样，其中肠道菌群可通过脑-肠轴途径影响宿主代谢、免疫等多个过程，进而与多种疾病的发生发展相关。多囊卵巢综合征（polycystic ovary syndrome，PCOS）患者肠道菌群的改变与其胰岛素抵抗、高雄激素血症、慢性炎症、代谢综合征等临床特征及并发症相关。近年研究表明肠道菌群也可能通过胆汁酸、短链脂肪酸、神经酰胺、三甲胺衍生物等肠道代谢产物影响PCOS的发病及病理过程。此外，也有部分研究探讨了应用粪便微生物群移植、补充益生菌和合生元等调节肠道菌群，以期为改善PCOS临床表现及相关并发症提供理论基础。

关键词: 多囊卵巢综合征, 胃肠道微生物组, 治疗, 代谢疾病, 肠道代谢物

Abstract:

Human gut microbiota is rich and diverse, among which gut microbiota can affect host metabolism, immunity and other processes through the brain-gut axis pathway, and then is related to the occurrence and development of a variety of diseases. The changes of intestinal flora in patients with polycystic ovary syndrome (PCOS) are related to clinical features and complications such as insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome. Recent studies have shown that intestinal flora may also affect the pathogenesis and pathological process of PCOS through intestinal metabolites such as bile acids, short-chain fatty acids, ceramides and trimethylamine derivatives. In addition, some studies have explored the application of fecal microbiota transplantation, supplementation of probiotics and synbiotics to regulate intestinal flora, in order to provide a theoretical basis for improving the clinical manifestations and related complications of PCOS.

Key words: Polycystic ovary syndrome, Gastrointestinal microbiome, Therapy, Metabolic diseases, Intestinal metabolites

周昕玥, 李宁, 魏林飞, 张学红. 肠道菌群及肠道代谢物与多囊卵巢综合征的关系[J]. 国际生殖健康/计划生育杂志, 2024, 43(1): 42-47.

ZHOU Xin-yue, LI Ning, WEI Lin-fei, ZHANG Xue-hong. The Relationship between Intestinal Flora, Intestinal Metabolites and Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(1): 42-47.

参考文献 37

[1]	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
[2]	Torres PJ, Siakowska M, Banaszewska B, et al. Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism[J]. J Clin Endocrinol Metab, 2018, 103(4):1502-1511. doi: 10.1210/jc.2017-02153. pmid: 29370410
[3]	Liu R, Zhang C, Shi Y, et al. Dysbiosis of Gut Microbiota Associated with Clinical Parameters in Polycystic Ovary Syndrome[J]. Front Microbiol, 2017, 8:324. doi: 10.3389/fmicb.2017.00324. pmid: 28293234
[4]	Ley RE. Gut microbiota in 2015: Prevotella in the gut: choose carefully[J]. Nat Rev Gastroenterol Hepatol, 2016, 13(2):69-70. doi: 10.1038/nrgastro.2016.4. pmid: 26828918
[5]	Zeng B, Lai Z, Sun L, et al. Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): a pilot study[J]. Res Microbiol, 2019, 170(1):43-52. doi: 10.1016/j.resmic.2018.09.002. pmid: 30292647
[6]	Li P, Shuai P, Shen S, et al. Perturbations in gut microbiota composition in patients with polycystic ovary syndrome: a systematic review and meta-analysis[J]. BMC Med, 2023, 21(1):302. doi: 10.1186/s12916-023-02975-8. pmid: 37559119
[7]	Tremellen K, Pearce K. Dysbiosis of Gut Microbiota (DOGMA)--a novel theory for the development of Polycystic Ovarian Syndrome[J]. Med Hypotheses, 2012, 79(1):104-112. doi: 10.1016/j.mehy.2012.04.016. pmid: 22543078
[8]	He F, Li Y. The gut microbial composition in polycystic ovary syndrome with insulin resistance: findings from a normal-weight population[J]. J Ovarian Res, 2021, 14(1):50. doi: 10.1186/s13048-021-00799-9. pmid: 33773586
[9]	Yang YL, Zhou WW, Wu S, et al. Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome[J]. Endocrinology, 2021, 162(10):bqab118. doi: 10.1210/endocr/bqab118.
[10]	Li Y, Zhu Y, Li D, et al. Depletion of gut microbiota influents glucose metabolism and hyperandrogenism traits of mice with PCOS induced by letrozole[J]. Front Endocrinol(Lausanne), 2023, 14:1265152. doi: 10.3389/fendo.2023.1265152.
[11]	Kelley ST, Skarra DV, Rivera AJ, et al. The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome[J]. PLoS One, 2016, 11(1):e0146509. doi: 10.1371/journal.pone.0146509.
[12]	Barroso A, Santos-Marcos JA, Perdices-Lopez C, et al. Neonatal exposure to androgens dynamically alters gut microbiota architecture[J]. J Endocrinol, 2020, 247(1):69-85. doi: 10.1530/JOE-20-0277. pmid: 32755996
[13]	Zhou J, Qiu X, Chen X, et al. Comprehensive Analysis of Gut Microbiota Alteration in the Patients and Animal Models with Polycystic Ovary Syndrome[J]. J Microbiol, 2023, 61(9):821-836. doi: 10.1007/s12275-023-00079-9. pmid: 37824034
[14]	Patel J, Chaudhary H, Rajput K, et al. Assessment of gut microbial β-glucuronidase and β-glucosidase activity in women with polycystic ovary syndrome[J]. Sci Rep, 2023, 13(1):11967. doi: 10.1038/s41598-023-39168-5. pmid: 37488157
[15]	Gao Y, Zou Y, Wu G, et al. Oxidative stress and mitochondrial dysfunction of granulosa cells in polycystic ovarian syndrome[J]. Front Med(Lausanne), 2023, 10:1193749. doi: 10.3389/fmed.2023.1193749.
[16]	Menchetti L, Barbato O, Filipescu IE, et al. Effects of local lipopolysaccharide administration on the expression of Toll-like receptor 4 and pro-inflammatory cytokines in uterus and oviduct of rabbit does[J]. Theriogenology, 2018, 107:162-174. doi: 10.1016/j.theriogenology.2017.10.046. pmid: 29161657
[17]	González F, Considine RV, Abdelhadi OA, et al. Saturated Fat Ingestion Promotes Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Polycystic Ovary Syndrome[J]. J Clin Endocrinol Metab, 2019, 104(3):934-946. doi: 10.1210/jc.2018-01143. pmid: 30590569
[18]	de la Cuesta-Zuluaga J, Huus KE, Youngblut ND, et al. Obesity is the main driver of altered gut microbiome functions in the metabolically unhealthy[J]. Gut Microbes, 2023, 15(2):2246634. doi: 10.1080/19490976.2023.2246634.
[19]	Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature, 2006, 444(7122):1027-1031. doi: 10.1038/nature05414.
[20]	张宁, 李菲, 李玲. 肠道菌群与多囊卵巢综合征关系的研究进展[J]. 国际妇产科学杂志, 2018, 45(1):101-105.
[21]	Pintarič M, Langerholc T. Probiotic Mechanisms Affecting Glucose Homeostasis: A Scoping Review[J]. Life(Basel), 2022, 12(8):1187. doi: 10.3390/life12081187.
[22]	Jia C, Xu H, Xu Y, et al. Serum metabolomics analysis of patients with polycystic ovary syndrome by mass spectrometry[J]. Mol Reprod Dev, 2019, 86(3):292-297. doi: 10.1002/mrd.23104. pmid: 30624822
[23]	Pathak P, Xie C, Nichols RG, et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism[J]. Hepatology, 2018, 68(4):1574-1588. doi: 10.1002/hep.29857. pmid: 29486523
[24]	Zhang B, Shen S, Gu T, et al. Increased circulating conjugated primary bile acids are associated with hyperandrogenism in women with polycystic ovary syndrome[J]. J Steroid Biochem Mol Biol, 2019, 189:171-175. doi: 10.1016/j.jsbmb.2019.03.005.
[25]	Gozukara I, Dokuyucu R, Özgür T, et al. Histopathologic and metabolic effect of ursodeoxycholic acid treatment on PCOS rat model[J]. Gynecol Endocrinol, 2016, 32(6):492-497. doi: 10.3109/09513590.2015.1134478. pmid: 26772475
[26]	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-e00019. doi: 10.1128/mSystems.00017-19.
[27]	Li T, Zhang T, Gao H, et al. Tempol ameliorates polycystic ovary syndrome through attenuating intestinal oxidative stress and modulating of gut microbiota composition-serum metabolites interaction[J]. Redox Biol, 2021, 41:101886. doi: 10.1016/j.redox.2021.101886.
[28]	Johnson EL, Heaver SL, Waters JL, et al. Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels[J]. Nat Commun, 2020, 11(1):2471. doi: 10.1038/s41467-020-16274-w. pmid: 32424203
[29]	Liu JL, Segovia I, Yuan XL, et al. Controversial Roles of Gut Microbiota-Derived Short-Chain Fatty Acids (SCFAs) on Pancreatic β-Cell Growth and Insulin Secretion[J]. Int J Mol Sci, 2020, 21(3):910. doi: 10.3390/ijms21030910.
[30]	He Y, Shi L, Qi Y, et al. Butylated starch alleviates polycystic ovary syndrome by stimulating the secretion of peptide tyrosine-tyrosine and regulating faecal microbiota[J]. Carbohydr Polym, 2022, 287:119304. doi: 10.1016/j.carbpol.2022.119304.
[31]	Kayser BD, Prifti E, Lhomme M, et al. Elevated serum ceramides are linked with obesity-associated gut dysbiosis and impaired glucose metabolism[J]. Metabolomics, 2019, 15(11):140. doi: 10.1007/s11306-019-1596-0. pmid: 31605240
[32]	Li J, Xie LM, Song JL, et al. Alterations of Sphingolipid Metabolism in Different Types of Polycystic Ovary Syndrome[J]. Sci Rep, 2019, 9(1):3204. doi: 10.1038/s41598-019-38944-6. pmid: 30824725
[33]	Heianza Y, Sun D, Li X, et al. Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial[J]. Gut, 2019, 68(2):263-270. doi: 10.1136/gutjnl-2018-316155. pmid: 29860242
[34]	Chen S, Henderson A, Petriello MC, et al. Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction[J]. Cell Metab, 2019, 30(6):1141-1151.e5. doi: 10.1016/j.cmet.2019.08.021. pmid: 31543404
[35]	Eyupoglu ND, Caliskan Guzelce E, Acikgoz A, et al. Circulating gut microbiota metabolite trimethylamine N-oxide and oral contraceptive use in polycystic ovary syndrome[J]. Clin Endocrinol(Oxf), 2019, 91(6):810-815. doi: 10.1111/cen.14101.
[36]	Cozzolino M, Vitagliano A, Pellegrini L, et al. Therapy with probiotics and synbiotics for polycystic ovarian syndrome: a systematic review and meta-analysis[J]. Eur J Nutr, 2020, 59(7):2841-2856. doi: 10.1007/s00394-020-02233-0. pmid: 32372265
[37]	Luo M, Chen Y, Pan X, et al. E. coli Nissle 1917 ameliorates mitochondrial injury of granulosa cells in polycystic ovary syndrome through promoting gut immune factor IL-22 via gut microbiota and microbial metabolism[J]. Front Immunol, 2023, 14:1137089. doi: 10.3389/fimmu.2023.1137089.