Gut microbiota-estrogen axis: Its influence on female health outcomes – A narrative review
Keywords:
gut microbiota, estrogen metabolism, dysbiosis, polycystic ovary syndrome, insulin resistance, female reproductive healthAbstract
Background: During women’s lifetime, gut microbiota plays roles in the reproductive endocrine system influencing hormones such as estrogen, androgens, insulin and other hormones. Gut microbiota trigger estrobolome to produce β-glucuronidase that deconjugates estrogens into their active forms. An imbalance in the microbiome affects microbial diversity, decreases estrogen deconjugation and reduces the circulating estrogen that leads to many diseases like polycystic ovary syndrome (PCOS) and diabetes. This study aims to review the studies that correlate estrogen, gut microbiota and female health. Material and methods: published research articles (period from 2018 to 2024) were assessed through Science Direct, PubMed, Scopus, and Google Scholar using these terms: gut microbiota, human, female health, estrogen, and estrobolome (total articles 78). Articles were selected and tracked to avoid any duplication by excluding animal studies articles, those with insufficient data, and those without interesting outcomes. Articles were selected that determine any association between gut microbiota, estrogen, and female health (total 12) as in Figure 1. Gut microbiota plays an important role in the women’s endocrine system, and β-glucuronidase is critical for estrogen metabolism. Distribution in estrogen metabolism causes gut microbial dysbiosis diseases, such as PCOS, obesity and diabetes. In post-menopausal women, high estrogen was associated with an increase in α-diversity microbiota. Lactobacillus was an abundant bacteria in pre and post-menopausal groups. Non-ovarian estrogens were associated with abundant microbiota that produce β-glucuronidase, such as Ruminococcaceae and Clostridia. This article reviews the previous studies about gut microbiota, estrogen, diabetes, obesity and PCOS. Conclusion: This review highlights the association between estrogen, gut microbiota diversity, diabetes, obesity and PCOS. Understanding the complex association between estrogen and the gut microbiota may attract attention to prevent and treat gastrointestinal disorders by microbiota modulation.
References
Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, et al. Microbiota in health and diseases. Signal Transduct Target Ther. 2022;7(1):135.
Wu Y, Feng X, Li M, Hu Z, Zheng Y, et al. Gut microbiota associated with appetite suppression in high-temperature and high-humidity environments. EBioMedicine. 2024;99:104918.
Margolis KG, Cryan JF, Mayer EA. The Microbiota-Gut-Brain Axis: From Motility to Mood. Gastroenterology. 2021;160(5):1486-1501.
Qi X, Yun C, Sun L, Xia J, Wu Q, et al. Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat Med. 2019; 25(8):1225–1233
Sun Y, Gao S, Ye C, Zhao W. Gut microbiota dysbiosis in polycystic ovary syndrome: Mechanisms of progression and clinical applications. Front Cell Infect Microbiol. 2023;13:1142041.
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010; 464(7285):59–21
Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies. Chem Rev. 2023;123(1):31-72.
Ma ZS, Li W. How and Why Men and Women Differ in Their Microbiomes: Medical Ecology and Network Analyses of the Microgenderome. Adv Sci (Weinh). 2019;6(23):1902054.
Kim N. Sexual Dimorphism in the Gut Microbiome: Microgenderome or Microsexome? Author's Reply. J Neurogastroenterol Motil. 2022;28(2):334
Qi X, Yun C, Pang Y, Qiao J. The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes. 2021 Jan-Dec;13(1):1-21.
Mazhar M, Zhu Y, Qin L. The Interplay of Dietary Fibers and Intestinal Microbiota Affects Type 2 Diabetes by Generating Short-Chain Fatty Acids. Foods. 2023;12(5):1023.
Abdul Rahim MBH, Chilloux J, Martinez-Gili L, Neves AL, Myridakis A, et al. Diet-induced metabolic changes of the human gut microbiome: importance of short-chain fatty acids, methylamines and indoles. Acta Diabetol. 2019;56(5):493-500.
Pearce SC, Karl JP, Weber GJ. Effects of short-chain fatty acids on intestinal function in an enteroid model of hypoxia. Front Physiol. 2022;13:1056233.
Chambers ES, Morrison DJ, Frost G. Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms? Proc Nutr Soc. 2015;74(3):328-36.
arabi AB, Masson HLP, Bäumler AJ. Bile acids as modulators of gut microbiota composition and function. Gut Microbes. 2023;15(1):2172671.
Appleton J. The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integr Med (Encinitas). 2018;17(4):28-32.
Vomstein K, Reider S, Böttcher B, Watschinger C, Kyvelidou C, et al. Uterine microbiota plasticity during the menstrual cycle: Differences between healthy controls and patients with recurrent miscarriage or implantation failure. J Reprod Immunol. 2022;151:103634.
Gorczyca K, Obuchowska A, Kimber-Trojnar Ż, Wierzchowska-Opoka M, Leszczyńska-Gorzelak B. Changes in the Gut Microbiome and Pathologies in Pregnancy. Int J Environ Res Public Health. 2022;19(16):9961.
Santacruz A, Collado MC, García-Valdés L, Segura MT, Martín-Lagos JA, et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr. 2010;104(1):83-92.
Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008;88(4):894-9.
Meng Q, Ma M, Zhang W, Bi Y, Cheng P, Yu X, Fu Y, Chao Y, Ji T, Li J, Chen Q, Zhang Q, Li Y, Shan J, Bian H. The gut microbiota during the progression of atherosclerosis in the perimenopausal period shows specific compositional changes and significant correlations with circulating lipid metabolites. Gut Microbes. 2021;13(1):1-27.
Park MG, Cho S, Oh MM. Menopausal Changes in the Microbiome-A Review Focused on the Genitourinary Microbiome. Diagnostics (Basel). 2023;13(6):1193.
Wang H, Liu J, Wu Z, Zhao Y, Cao M, Shi B, Chen B, Chen N, Guo H, Li N, Chen J, Xu R. Gut microbiota signatures and fecal metabolites in postmenopausal women with osteoporosis. Gut Pathog. 2023;15(1):33.
Hu S, Ding Q, Zhang W, Kang M, Ma J, Zhao L. Gut microbial beta-glucuronidase: a vital regulator in female estrogen metabolism. Gut Microbes. 2023 Jan-Dec;15(1):2236749.
Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe. 2011;10(4):324-35.
Wei Z, Yang B, Tang T, Xiao Z, Ye F, et al. Gut microbiota and risk of five common cancers: A univariable and multivariable Mendelian randomization study. Cancer Med. 2023;12(9):10393-10405.
Persson I. Estrogens in the causation of breast, endometrial and ovarian cancers - evidence and hypotheses from epidemiological findings. J Steroid Biochem Mol Biol. 2000 ;74(5):357-64.
Goedert JJ, Hua X, Bielecka A, Okayasu I, Milne GL, et al. Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-noncoated faecal microbiota. Br J Cancer. 2018;118(4):471-479.
Hussain T, Murtaza G, Kalhoro DH, Kalhoro MS, Metwally E, et al. Relationship between gut microbiota and host-metabolism: Emphasis on hormones related to reproductive function. Anim Nutr. 2021;7(1):1-10.
Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016;2:16057.
Insenser M, Murri M, Del Campo R, Martínez-García MÁ, Fernández-Durán E, et al. Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity. J Clin Endocrinol Metab. 2018;103(7):2552-2562.
Zheng Y, Yu J, Liang C, Li S, Wen X, et al. Characterization on gut microbiome of PCOS rats and its further design by shifts in high-fat diet and dihydrotestosterone induction in PCOS rats. Bioprocess Biosyst Eng. 2021;44(5):953-964.
Shin JH, Park YH, Sim M, Kim SA, Joung H, et al. Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome. Res Microbiol. 2019;170(4-5):192-201.
Sherman SB, Sarsour N, Salehi M, Schroering A, Mell B, et al. Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis. Gut Microbes. 2018;9(5):400-421.
Doden HL, Ridlon JM. Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega. Microorganisms. 2021;9(3):469.
Yang YY, Pereyra LP, Young RB, Reardon KF, Borch T. Testosterone-mineralizing culture enriched from swine manure: characterization of degradation pathways and microbial community composition. Environ Sci Technol. 2011;45(16):6879-86.
Xiao L, Sonne SB, Feng Q, Chen N, Xia Z, et al. High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice. Microbiome. 2017;5(1):43.
Alemany M. Estrogens and the regulation of glucose metabolism. World J Diabetes. 2021;12(10):1622-1654.
Acharya KD, Noh HL, Graham ME, Suk S, Friedline RH, et al. Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice. Metabolites. 2021;11(8):499.
Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017;103:45-53.
. Łoniewski I, Szulińska M, Kaczmarczyk M, Podsiadło K, Styburski D, et al. Analysis of correlations between gut microbiota, stool short chain fatty acids, calprotectin and cardiometabolic risk factors in postmenopausal women with obesity: a cross-sectional study. J Transl Med. 2022;20(1):585.
Santos-Marcos JA, Rangel-Zuñiga OA, Jimenez-Lucena R, Quintana-Navarro GM, Garcia-Carpintero S, et al. Influence of gender and menopausal status on gut microbiota. Maturitas. 2018;116:43-53.
Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008;105(43):16767-72.
Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61(2):364-71.
Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018 May;14(5):270-284.
Szukiewicz D, Trojanowski S, Kociszewska A, Szewczyk G. Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)-Searching for Epigenetic Factors. Int J Mol Sci. 2022;23(23):14663.
Min Q, Geng H, Gao Q, Xu M. The association between gut microbiome and PCOS: evidence from meta-analysis and two-sample mendelian randomization. Front Microbiol. 2023;14:1203902.
Sola-Leyva A, Pérez-Prieto I, Molina NM, Vargas E, Ruiz-Durán S, et al. Microbial composition across body sites in polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biomed Online. 2023;47(1):129-150.
Kelley ST, Skarra DV, Rivera AJ, Thackray VG. The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome. PLoS One. 2016 ;11(1):e0146509.
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(1):63-73.
Wang L, Zhou J, Gober HJ, Leung WT, Huang Z, et al. Alterations in the intestinal microbiome associated with PCOS affect the clinical phenotype. Biomed Pharmacother. 2021;133:110958.
Guo Y, Qi Y, Yang X, Zhao L, Wen S, et al. Association between Polycystic Ovary Syndrome and Gut Microbiota. PLoS One. 2016;11(4):e0153196.
Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007 Nov;50(11):2374-83.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Manar Atoum, Kanchi Padma
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
How to Cite
