https://doi.org/10.4081/jbr.2026.14711
Microbiome, probiotics and lifestyle modulation in women’s health across the lifespan: endocrine, immune, and microbial interconnections
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Published: 15 July 2026
Hormonal fluctuations throughout a woman’s life, from puberty to menopause, profoundly influence the composition of the vaginal and gut microbiota, with major implications for reproductive, metabolic, and psychological health. Recent findings indicate that lifestyle factors, such as diet, stress, sleep, and physical activity, modulate microbial communities and hormonal balance through an integrated microbiome–immune–endocrine axis. This review examines the evolution of the vaginal microbiota, the effects of hormonal changes on microbial balance, and evidence for probiotic and lifestyle-based interventions in conditions such as bacterial vaginosis, endometriosis, polycystic ovary syndrome, pregnancy complications, and menopausal disorders. Particular attention is given to the estrobolome, gut–brain communication, and metabolic regulators as mediators of systemic effects.
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1. Barraza-Ortega E, Gómez-Gil B, García-Gasca T, et al. The impact of lifestyle on reproductive health: microbial complexity, hormonal dysfunction, and pregnancy outcomes. Int J Mol Sci 2025;26:8574. DOI: https://doi.org/10.3390/ijms26178574
2. Tachedjian G, Aldunate M, Bradshaw CS, et al. The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol 2017;168:782–92. DOI: https://doi.org/10.1016/j.resmic.2017.04.001
3. Falk P, Bishen S. Closing the women’s health gap: a $1 trillion opportunity to improve lives and economies. World Economic Forum. 2024. Available from: https://www.weforum.org/stories/2024/01/women-healthcare-gap/?gad_source=1&gad_campaignid=22228224717&gbraid=0AAAAAoVy5F6ET23g5VWPjJPxEpj4Er0gN&gclid=Cj0KCQjwiJvQBhCYARIsAMjts3J8L0yITresJCTrEWhOztUs6HaxYPzPEG56jVt5yWvtTHICFaIz2HgaAvDmEALw_wcB
4. National Institutes of Health. Women’s Health. https://www.nichd.nih.gov/health/topics/womenshealth (accessed February 19, 2025).
5. U.S. Food and Drug Administration. Department of Health and Human Services. Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs. July 22, 1993.
6. Pinnow E, Sharma P, Parekh A, et al. Increasing participation of women in early-phase clinical trials approved by the FDA. Womens Health Issues 2009;19:89–93. DOI: https://doi.org/10.1016/j.whi.2008.09.009
7. Sosinsky AZ, Rich-Edwards JW, Wiley A, et al. Enrollment of female participants in US phase 1–3 clinical trials between 2016 and 2019. Contemp Clin Trials 2022;115:106718. DOI: https://doi.org/10.1016/j.cct.2022.106718
8. Krakowsky Y, Potter E, Hallarn J, et al. The effect of gender-affirming medical care on the vaginal and neovaginal microbiomes of transgender and gender-diverse people. Front Cell Infect Microbiol 2022;11:769950. DOI: https://doi.org/10.3389/fcimb.2021.769950
9. Chen Z, Yeoh YK, Hui M, et al. Diversity of macaque microbiota compared to human counterparts. Sci Rep 2018;8:15573. DOI: https://doi.org/10.1038/s41598-018-33950-6
10. Miller EA, Beasley DE, Dunn RR, et al. Lactobacilli dominance and vaginal pH: Why is the human vaginal microbiome unique? Front Microbiol 2016;7:1936. DOI: https://doi.org/10.3389/fmicb.2016.01936
11. Miller EA, Livermore JA, Alberts SC, et al. Ovarian cycling and reproductive state shape the vaginal microbiota in wild baboons. Microbiome 2017;5:8. DOI: https://doi.org/10.1186/s40168-017-0228-z
12. Mirmonsef P, Hotton AL, Gilbert D, et al. Free glycogen in vaginal fluids is associated with Lactobacilluscolonization and low vaginal pH. PLoS ONE 2014;9:e102467. DOI: https://doi.org/10.1371/journal.pone.0102467
13. Spear GT, French AL, Gilbert D, et al. Human α-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus. J Infect Dis 2014;210:1019–28. DOI: https://doi.org/10.1093/infdis/jiu231
14. Jenkins DJ, Woolston BM, Hood-Pishchany MI, et al. Bacterial amylases enable glycogen degradation by the vaginal microbiome. Nat Microbiol 2023;8:1641–52. DOI: https://doi.org/10.1038/s41564-023-01447-2
15. Kwon MS, Lee HK. Host and microbiome interplay shapes the vaginal microenvironment. Front Immunol. 2022;13:919728. DOI: https://doi.org/10.3389/fimmu.2022.919728
16. Frederiksen H, Johannsen TH, Andersen SE, et al. Sex-specific estrogen levels and reference intervals from infancy to late adulthood determined by LC-MS/MS. J Clin Endocrinol Metab 2019;105:754–68. DOI: https://doi.org/10.1210/clinem/dgz196
17. Hickey RJ, Zhou X, Settles ML, et al. Vaginal microbiota of adolescent girls prior to menarche resembles that of reproductive-age women. mBio 2015;6:e00097-15. DOI: https://doi.org/10.1128/mBio.00097-15
18. Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA 2011;108:4680–4687. DOI: https://doi.org/10.1073/pnas.1002611107
19. Petrova MI, Reid G, Vaneechoutte M, Lebeer S. Lactobacillus iners: friend or foe? Trends Microbiol 2017;25:182–91. DOI: https://doi.org/10.1016/j.tim.2016.11.007
20. Saperston KN, Shapiro DJ, Hersh AL, Copp HL. A comparison of inpatient versus outpatient resistance patterns of pediatric urinary tract infection pathogens. Pediatrics 2014;133:e123–8.
21. Ma B, Forney LJ, Ravel J. Vaginal microbiome: rethinking health and disease. Annu Rev Microbiol 2012;66:371–89. DOI: https://doi.org/10.1146/annurev-micro-092611-150157
22. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T 2015;40:277–83.
23. De Clercq M, Van Hoorde K, Fiddelaers J, et al. The Isala citizen science project on the vaginal microbiome of 3,345 Belgian women. Nat Microbiol 2023;8:1378–91.
24. Kenyon C, Colebunders R, Crucitti T. The global epidemiology of bacterial vaginosis: a systematic review. Am J Obstet Gynecol 2013;209:505–23. DOI: https://doi.org/10.1016/j.ajog.2013.05.006
25. Muzny CA, Taylor CM, Swords WE, et al. An updated conceptual model on the pathogenesis of bacterial vaginosis. J Infect Dis 2019;220:1399–405. DOI: https://doi.org/10.1093/infdis/jiz342
26. Nel Van Der Veer C, et al. Comparative activity of L. crispatus strains against Gardnerella and Prevotella. Microbiome 2022;10:51.
27. Huang H, Song L, Zhao W, et al. Probiotics for the treatment of bacterial vaginosis: a systematic review and meta-analysis. Front Cell Infect Microbiol 2022;12:827636.
28. Senok AC, Verstraelen H, Temmerman M, Botta GA. Probiotics for the treatment of bacterial vaginosis. Cochrane Database Syst Rev 2009;4:CD006289. DOI: https://doi.org/10.1002/14651858.CD006289.pub2
29. Brusselaers N, Shrestha S, van de Wijgert J, Verstraelen H. Vaginal dysbiosis and gynecological cancers: a review. Front Cell Infect Microbiol 2019;9:290. DOI: https://doi.org/10.1016/j.ajog.2018.12.011
30. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen–gut microbiome axis: physiological and clinical implications. Maturitas 2017;103:45–53. DOI: https://doi.org/10.1016/j.maturitas.2017.06.025
31. Kwa M, Plottel CS, Blaser MJ, Adams S. The intestinal microbiome and estrogen receptor–positive female breast cancer. J Natl Cancer Inst 2016;108:djw029.
32. Fuhrman BJ, Feigelson HS, Flores R, et al. Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women. J Clin Endocrinol Metab 2014;99:4632–40. DOI: https://doi.org/10.1210/jc.2014-2222
33. Meng S, Chen B, Yang J, et al. Gut microbiota and breast cancer: correlations, mechanisms and potential clinical implications. Front Oncol 2021;11:706003.
34. Zhu J, Liao M, Yao Z, et al. The role of gut microbiota in postmenopausal osteoporosis. Front Cell Infect Microbiol 2022;12:819541.
35. Mitra A, MacIntyre DA, Marchesi JR, et al. The vaginal microbiota, human papillomavirus infection, and cervical intraepithelial neoplasia: what do we know and where are we going next? Microbiome 2016;4:58. DOI: https://doi.org/10.1186/s40168-016-0203-0
36. Liu CM, Hungate BA, Tobian AA, et al. Penile microbiota and female partner bacterial vaginosis in Rakai, Uganda. mBio 2015;6:e00589–15. DOI: https://doi.org/10.1128/mBio.00589-15
37. Onywera H, Williamson AL, Mbulawa ZZA, et al. The penile microbiota in uncircumcised and circumcised men: relationships with HIV and HPV infections. Front Public Health 2020;8:7. DOI: https://doi.org/10.3389/fmed.2020.00383
38. Clarke G, Stilling RM, Kennedy PJ, et al. Minireview: gut microbiota: the neglected endocrine organ. Mol Endocrinol 2014;28:1221–38. DOI: https://doi.org/10.1210/me.2014-1108
39. Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol 2015;11:577–91. DOI: https://doi.org/10.1038/nrendo.2015.128
40. Knezevic J, Starchl C, Berisha AT, Amrein K. Thyroid-gut-axis: how does the intestinal microbiota influence thyroid function? Nutrients 2020;12:1769. DOI: https://doi.org/10.3390/nu12061769
41. Brotman RM, Shardell MD, Gajer P, et al. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 2018;25:1321–330. DOI: https://doi.org/10.1097/GME.0000000000001236
42. Song SD, Acharya KD, Zhu JE, et al. Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome 2020;8:1–20.
43. Romero R, Hassan SS, Gajer P, et al. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome 2014;2:4. DOI: https://doi.org/10.1186/2049-2618-2-10
44. Serrano MG, Brotman RM, Ravel J. The vaginal microbiome: new insights into the pathogenesis of bacterial vaginosis and vaginitis. Curr Opin Infect Dis 2022;35:73–9.
45. Moen MH, Øian P, Mellembakken JR, et al. Vaginal microbiota dynamics in young women—associations with hormones, contraceptives, and sexual behavior. Front Cell Infect Microbiol 2024;14:1314521.
46. Fettweis JM, Serrano MG, Brooks JP, et al. The vaginal microbiome and preterm birth. Nat Med 2019;25:1012–21. DOI: https://doi.org/10.1038/s41591-019-0450-2
47. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med 2020;382:1244–56. DOI: https://doi.org/10.1056/NEJMra1810764
48. Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397:839–852. DOI: https://doi.org/10.1016/S0140-6736(21)00389-5
49. Chapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol 2019;15:666–82. DOI: https://doi.org/10.1038/s41574-019-0245-z
50. Parazzini F, Viganò P, Candiani M, Fedele L. Diet and endometriosis risk: a literature review. Reprod Biomed Online 2013;26:323–36. DOI: https://doi.org/10.1016/j.rbmo.2012.12.011
51. Nirgianakis K, Egger K, Kalaitzopoulos DR, et al. Effect of omega-3 supplementation in endometriosis-related pain: a randomized controlled trial. Fertil Steril 2020;113:1209–17.
52. Itoh H, Uchida M, Sashihara T, et al. Oral administration of heat-killed Lactobacillus gasseri improves symptoms of endometriosis: a randomized trial. J Obstet Gynaecol Res. 2021;47:2761–70.
53. Uchida M, Kobayashi O, Itoh H. Oral administration of heat-killed L. gasseri alleviates endometriosis-like lesions in mice. J Med Microbiol 2020;69:1035–44.
54. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018;14:270–84. DOI: https://doi.org/10.1038/nrendo.2018.24
55. Lindheim L, Bashir M, Munzker J, et al. Alterations in gut microbiome composition and barrier function in PCOS: a pilot study. PLoS ONE 2017;12:e0168390. DOI: https://doi.org/10.1371/journal.pone.0168390
56. Torres PJ, Siakowska M, Banaszewska B, et al. Gut microbial diversity in women with PCOS correlates with hyperandrogenism. J Clin Endocrinol Metab 2018;103:1502–11. DOI: https://doi.org/10.1210/jc.2017-02153
57. Yurtdaş G, Akdevelioğlu Y. A new perspective on PCOS: the gut microbiota. J Turk Ger Gynecol Assoc 2020;21:153–64.
58. Shoaei T, Heidari-Beni M, Tabrizi R, et al. The effects of probiotics on metabolic outcomes in women with PCOS: a systematic review and meta-analysis. Nutrients 2023;15:3184.
59. Chen L, Ma F, Lu W, et al. Effects of synbiotics on hormonal and inflammatory parameters in women with PCOS: a systematic review. Front Endocrinol (Lausanne) 2022;13:869187.
60. Aagaard K, Ma J, Antony KM, et al. The placenta harbors a unique microbiome. Sci Transl Med 2014;6:237ra65. DOI: https://doi.org/10.1126/scitranslmed.3008599
61. Brown RG, Marchesi JR, Lee YS, et al. Vaginal dysbiosis increases preterm birth risk. Microbiome 2018;6:117. DOI: https://doi.org/10.1186/s40168-018-0502-8
62. Brown RG, Al-Memar M, Marchesi JR, et al. Preterm birth, bacterial vaginosis, and neonatal outcomes: a cohort study. Am J Obstet Gynecol 2022;226:91.e1–91.e14.
63. Haahr T, Zacho J, Bräuner M, et al. Vaginal microbiota and IVF outcomes: a prospective study. Hum Reprod 2019;34:1369–79.
64. Kyono K, Hashimoto T, Nagai Y, et al. Endometrial microbiota and IVF outcomes: a pilot study. Reprod Med Biol 2018;17:481–6. DOI: https://doi.org/10.1002/rmb2.12105
65. Fettweis JM, Serrano MG, Brooks JP, et al. Association between vaginal dysbiosis and recurrent pregnancy loss. Reprod Sci 2020;27:132–40.
66. Moreno I, Codoñer FM, Vilella F, et al. Evidence that the endometrial microbiota has an impact on implantation success or failure. Am J Obstet Gynecol 2016;215:684–703. DOI: https://doi.org/10.1016/j.ajog.2016.09.075
67. Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA. 2010;107:11971–5. DOI: https://doi.org/10.1073/pnas.1002601107
68. Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med 2016;22:713–22. DOI: https://doi.org/10.1038/nm.4142
69. Vicariotto F, Mogna L, Del Piano M. Clinical evidence for probiotics in preventing perinatal depression. Minerva Ginecol 2020;72:280–9.
70. Slykerman RF, Hood F, Wickens K, et al. Probiotic during pregnancy and postpartum depression: randomized trial. EBioMedicine 2017;24:159–65. DOI: https://doi.org/10.1016/j.ebiom.2017.09.013
71. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5th ed. Washington, DC; 2013. DOI: https://doi.org/10.1176/appi.books.9780890425596
72. O’Hara MW, Wisner KL. Perinatal mental illness: definition, description and aetiology. Best Pract Res Clin Obstet Gynaecol 2014;28:3–12. DOI: https://doi.org/10.1016/j.bpobgyn.2013.09.002
73. Dennis CL, Falah-Hassani K, Shiri R. Prevalence of antenatal and postnatal anxiety: systematic review and meta-analysis. Br J Psychiatry 2017;210:315–23. DOI: https://doi.org/10.1192/bjp.bp.116.187179
74. Huang H, Song L, Zhao W, et al. The impact of menopause on vaginal microbiota. Front Cell Infect Microbiol 2023;13:1181945.
75. Nappi RE, Palacios S. Impact of vulvovaginal atrophy on sexual health. Maturitas 2014;78:236–40.
76. Gandhi J, Chen A, Dagur G, et al. Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol 2016;215:704–11. DOI: https://doi.org/10.1016/j.ajog.2016.07.045
77. Chen J, Geng S, Li Z, et al. Effect of Lactobacillus rhamnosus GR-1 and L. brevis on genitourinary syndrome of menopause: randomized controlled trial. Menopause 2020;27:914–23.
78. Kim H, Kim H, Park H, et al. Oral probiotics for postmenopausal women: effects on vaginal health and systemic inflammation. Nutrients 2022;14:1589. DOI: https://doi.org/10.3390/nu14142982
79. Kim MJ, Chung J, Kim DH, Kwon OJ. The effect of Lactobacillus acidophilus YT1 (MENOLACTO) on improving menopausal symptoms: a randomized, double-blinded, placebo-controlled clinical trial. J Clin Med 2020;9:2173. DOI: https://doi.org/10.3390/jcm9072173
80. Palma F, Volpe A, Villa P, Cagnacci A. Vaginal Lactobacillus acidophilus plus low-dose estriol for postmenopausal atrophy: randomized controlled study. Climacteric 2016;19:444–50.
81. Marschalek J, Worda C, Kohlberger P, et al. Influence of oral and vaginal Lactobacilli supplementation on the bacterial vaginosis-related vaginal microbiome in perimenopausal women undergoing chemotherapy for breast cancer. Front Oncol 2022;12:785856.
82. Li J, Wu J, Zhou Y, et al. Effects of probiotics on bone metabolism in postmenopausal women: systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024;15:1367914. DOI: https://doi.org/10.3389/fendo.2024.1487998
83. Chen J, Kannan S, Tan Y, et al. Human vaginal organoids: a new platform to study host–microbe interactions. Cell Rep 2022;38:110300.
84. Das Neves J, Sarmento B. Vaginal mucosa-on-a-chip: future directions for drug and microbiome research. Adv Drug Deliv Rev 2021;175:113818.
85. Li X, Zhou T, Zhu Y, et al. Vaginal epithelium–microbiome crosstalk model reveals metabolic regulation of dysbiosis. Nat Commun. 2023;14:2294.
86. Hill C, Guarner F, Reid G, et al. Expert consensus on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11:506–14. DOI: https://doi.org/10.1038/nrgastro.2014.66
87. European Food Safety Authority (EFSA). Qualified Presumption of Safety (QPS) Approach for Assessment of Microorganisms. EFSA J 2020;18:e05968.
88. Marco ML, Heeney D, Binda S, et al. Health benefits of fermented foods: microbiota and beyond. Nat Rev Gastroenterol Hepatol 2021;18:608–23.
89. Romeo M, D’Urso F, Ciccarese G, et al. Exploring oral and vaginal probiotic solutions for women’s health from puberty to menopause: a narrative review. Microorganisms 2024;12:1614. DOI: https://doi.org/10.3390/microorganisms12081614
90. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the prevention of ovulatory disorder infertility. Obstet Gynecol 2007;110:1050–8. DOI: https://doi.org/10.1097/01.AOG.0000287293.25465.e1
91. Cryan JF, O’Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev 2019;99:1877–2013. DOI: https://doi.org/10.1152/physrev.00018.2018
92. Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol 2017;14:491–502. DOI: https://doi.org/10.1038/nrgastro.2017.75
93. Gore AC, Chappell VA, Fenton SE, et al. EDC-2: The Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev 2015;36:E1–E150. DOI: https://doi.org/10.1210/er.2015-1010
94. Smith RP, Easson C, Lyle SM, et al. Gut microbiome diversity is associated with sleep physiology in humans. PLoS ONE 2019;14:e0222394. DOI: https://doi.org/10.1371/journal.pone.0222394
95. Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 2004;1:e62. DOI: https://doi.org/10.1371/journal.pmed.0010062
96. D’Urso F, Paladini F, Pollini M, Broccolo F. Use of Artificial Intelligence Chatbots in Interpretation of Clinical Chemistry and Laboratory Medicine Reports: A Standardized Approach. Appl Sci 2025;15:4232. DOI: https://doi.org/10.3390/app15084232
97. Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021;18:649–67. DOI: https://doi.org/10.1038/s41575-021-00440-6
98. Mailing LJ, Allen JM, Buford TW, Fields CJ, Woods JA. Exercise and the gut microbiome: a review of the evidence, potential mechanisms and implications for human health. Exerc Sport Sci Rev. 2019;47:75–85. DOI: https://doi.org/10.1249/JES.0000000000000183
99. Willing BP, Russell SL, Finlay BB. Shifting the balance: antibiotic effects on host-microbiota mutualism. Nat Rev Microbiol. 2011;9:233–43. DOI: https://doi.org/10.1038/nrmicro2536
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