From Gut to Reproductive Health: Exploring Microbiome Interactions and Future Interventions

Recent advances in microbiome research have illuminated the complex bidirectional interactions between gut health and reproductive well-being. Understanding the gut microbiome’s influence on the reproductive system and vice versa reveals how both of them can affect hormone production, immune function, and ultimately overall reproductive health. Dysbiosis, an imbalance in the gut microbial community, has been linked with a range of reproductive issues, including decreased sperm count and motility, erectile dysfunction, polycystic ovary syndrome (PCOS), endometriosis, infertility, and adverse pregnancy outcomes. This review critically evaluates emerging therapeutic interventions aimed at restoring microbial balance and enhancing reproductive health, such as use of prebiotics, probiotics, bacteriophage therapy, and fecal microbiota transplantation (FMT). By exploring the intricate interplay between gut microbiota and reproductive health, this review also emphasizes the need for integrated approaches in research and clinical practice to develop effective microbiome-based therapies for better reproductive health outcomes. Similar content being viewed by others Data Availability NA.

Acharya A, Shetty SS. Role of gut microbiota derived short chain fatty acid metabolites in modulating female reproductive health. Human Nutrition & Metabolism; 2024. p. 200256. Singh S, et al. Impact of environmental pollutants on gut microbiome and mental health via the gut–brain axis. Microorganisms. 2022;10(7):1457. Wang Y, Xie Z. Exploring the role of gut microbiome in male reproduction. Andrology. 2022;10(3):441–50. Qi X, et al. The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes. 2021;13(1):1894070. Chadchan SB, Singh V, Kommagani R. Female reproductive dysfunctions and the gut microbiota. J Mol Endocrinol. 2022;69(3):R81–94. Franasiak JM, Scott RT Jr. Reproductive tract microbiome in assisted reproductive technologies. Fertil Steril. 2015;104(6):1364–71. Green KA, Zarek SM, Catherino WH. Gynecologic health and disease in relation to the microbiome of the female reproductive tract. Fertil Steril. 2015;104(6):1351–7. Rea D, et al. Microbiota effects on cancer: from risks to therapies. Oncotarget. 2018;9(25):17915. Lundy SD, et al. Functional and taxonomic dysbiosis of the gut, urine, and semen microbiomes in male infertility. Eur Urol. 2021;79(6):826–36. Rowe M, et al. The reproductive microbiome: an emerging driver of sexual selection, sexual conflict, mating systems, and reproductive isolation. Trends Ecol Evol. 2020;35(3):220–34. Heil BA, Paccamonti DL, Sones JL. Role for the mammalian female reproductive tract microbiome in pregnancy outcomes. Physiol Genomics. 2019;51(8):390–9. Koedooder R, et al. Identification and evaluation of the microbiome in the female and male reproductive tracts. Hum Reprod Update. 2018;25(3):298–325. Feng T, Liu Y. Microorganisms in the reproductive system and probiotic’s regulatory effects on reproductive health. Comput Struct Biotechnol J. 2022;20:1541–53. Schoenmakers S, Steegers-Theunissen R, Faas M. The matter of the reproductive microbiome. Obstet Med. 2019;12(3):107–15. Tremellen K, Pearce K. Dysbiosis of gut microbiota (DOGMA)–a novel theory for the development of polycystic ovarian syndrome. Med Hypotheses. 2012;79(1):104–12. Mirmonsef P, et al. The effects of commensal bacteria on innate immune responses in the female genital tract. Am J Reprod Immunol. 2011;65(3):190–5. Bodelon C, et al. Genetic variation in the TLR and NF-κB pathways and cervical and vulvar cancer risk: a population‐based case–control study. Int J Cancer. 2014;134(2):437–44. Fuhrman BJ, et al. Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women. J Clin Endocrinol Metab. 2014;99(12):4632–40. Guo Y, et al. Association between polycystic ovary syndrome and gut microbiota. PLoS ONE. 2016;11(4):e0153196. Yuan M, et al. Endometriosis induces gut microbiota alterations in mice. Hum Reprod. 2018;33(4):607–16. Łaniewski P, Ilhan ZE, Herbst-Kralovetz MM. The microbiome and gynaecological cancer development, prevention and therapy. Nat Rev Urol. 2020;17(4):232–50. Qiu J-R, et al. Effect of ejiao (asini corii colla) and turtle carapace glue on gut microbiota in nude mice with uterine fibroids based on high-throughput sequencing of 16SrRNA gene. Evid Based Complement Alternat Med. 2022;2022:3934877. Singh S, et al. Polycystic ovary syndrome: etiology, current management, and future therapeutics. J Clin Med. 2023;12(4):1454. Pushkarna S, et al. Role of microbiome in reproductive health: an expanding dimension. In: Sobti R, Kuhad RC, Lal R, Rishi P, editors. Role of microbes in sustainable development: human health and diseases. Springer, Singapore; 2023. p. 361–94. Backhed F, et al. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915–20. Browne HP, et al. Transmission of the gut microbiota: spreading of health. Nat Rev Microbiol. 2017;15(9):531–43. Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533. Ashonibare VJ, et al. Gut microbiota-gonadal axis: the impact of gut microbiota on reproductive functions. Front Immunol. 2024;15:1346035. Arumugam M, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80. Rinninella E, et al. What is the healthy gut microbiota composition. A changing ecosystem across age, environment, diet, and diseases. Microorganisms. 2019;7:14. Haro C, et al. Intestinal microbiota is influenced by gender and body mass index. PLoS ONE. 2016;11(5):e0154090. Gloux K, et al. A metagenomic β-glucuronidase uncovers a core adaptive function of the human intestinal microbiome. Proc Natl Acad Sci U S A. 2011;108(supplement1):4539–46. Choi S, et al. Difference in the gut microbiome between ovariectomy-induced obesity and diet-induced obesity. J Microbiol Biotechnol. 2017;27(12):2228–36. Cristofori F, et al. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front Immunol. 2021;12:578386. Madere FS, Monaco CL. The female reproductive tract virome: understanding the dynamic role of viruses in gynecological health and disease. Curr Opin Virol. 2022;52:15–23. Punzón-Jiménez P, Labarta E. The impact of the female genital tract microbiome in women health and reproduction: a review. J Assist Reprod Genet. 2021;38(10):2519–41. Gao H, et al. Deciphering the role of female reproductive tract microbiome in reproductive health: a review. Front Cell Infect Microbiol. 2024;14:1351540. Baker JM, Chase DM, Herbst-Kralovetz MM. Uterine microbiota: residents, tourists, or invaders? Front Immunol. 2018;9:208. Salary A, et al. Detection of bacteria in bovine ovarian follicular fluid. Lett Appl Microbiol. 2020;70(3):137–42. Chen C, et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8:875. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen–gut microbiome axis: physiological and clinical implications. Maturitas. 2017;103:45–53. Tomaiuolo R, et al. Microbiota and human reproduction: the case of female infertility. High-throughput. 2020;9(2):12. Pelzer ES, et al. Microorganisms within human follicular fluid: effects on IVF. PLoS ONE. 2013;8(3):e59062. Ravel J, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011;108(supplement1):4680–7. Miller EA, et al. Lactobacilli dominance and vaginal pH: why is the human vaginal microbiome unique? Front Microbiol. 2016;7:1936. Bhattacharya K, et al. Reproductive tract microbiome and therapeutics of infertility. Middle East Fertil Soc J. 2023;28(1):11. Ma B, Forney LJ, Ravel J. Vaginal microbiome: rethinking health and disease. Annu Rev Microbiol. 2012;66(1):371–89. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000;342(20):1500–7. Hyman RW, et al. Diversity of the vaginal microbiome correlates with preterm birth. Reprod Sci. 2014;21(1):32–40. Gupta S, Kakkar V, Bhushan I. Crosstalk between vaginal microbiome and female health: a review. Microb Pathog. 2019;136:103696. Franasiak JM, Scott RT Jr. Introduction: Microbiome in human reproduction. Fertil Steril. 2015;104(6):1341–3. Moreno I, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215(6):684–703. Moreno I, et al. Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome. 2022;10:1–17. Kiecka A, Macura B, Szczepanik M. Can Lactobacillus spp. be a factor reducing the risk of miscarriage? Pol J Microbiol. 2021;70(4):431-446. Sobstyl M, et al. The role of microbiota in the immunopathogenesis of endometrial cancer. Int J Mol Sci. 2022;23(10):5756. Lingasamy P, et al. Exploring immunome and microbiome interplay in reproductive health: current knowledge, challenges, and novel diagnostic tools. Semin Reprod Med. 2023. https://doi.org/10.1055/s-0043-1778017. Miles SM, Hardy BL, Merrell DS. Investigation of the microbiota of the reproductive tract in women undergoing a total hysterectomy and bilateral salpingo-oopherectomy. Fertil Steril. 2017;107(3):813–20. e1. Chen C, et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8(1):875. Brennan C et al. Harnessing the power within: engineering the Microbiome for enhanced gynecologic health. Reprod Fertility, 2024;5(2). https://doi.org/10.1530/RAF-23-0060 Neto FTL, et al. Effect of environmental factors on seminal microbiome and impact on sperm quality. Front Endocrinol. 2024;15:1348186. Weng S-L, et al. Bacterial communities in semen from men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota to semen quality. PLoS ONE. 2014;9(10):e110152. Yan Y-Q, et al. Optimum doses and forms of selenium maintaining reproductive health via regulating homeostasis of gut microbiota and testicular redox, inflammation, cell proliferation, and apoptosis in roosters. J Nutr. 2024;154(2):369–80. Alfano M, et al. Testicular microbiome in azoospermic men—first evidence of the impact of an altered microenvironment. Hum Reprod. 2018;33(7):1212–7. Wilharm A, et al. Microbiota-dependent expansion of testicular IL-17-producing Vγ6 + γδ T cells upon puberty promotes local tissue immune surveillance. Mucosal Immunol. 2021;14(1):242–52. Jendraszak M, Skibińska I, Kotwicka M, Andrusiewicz M. The elusive male microbiome: revealing the link between the genital microbiota and fertility. Critical review and future perspectives. Crit Rev Clin Lab Sci. 2024;61(7):559–587. https://doi.org/10.1080/10408363.2024.2331489 Vajpeyee M, Tiwari S, Yadav LB. Characterization of seminal microbiome associated with semen parameters using next-generation sequencing. Middle East Fertil Soc J. 2024;29(1):22. Wang S, et al. Bacterial infections affect male fertility: a focus on the oxidative stress-autophagy axis. Front Cell Dev Biol. 2021;9:727812. Vitale SG, et al. The role of genital tract microbiome in fertility: a systematic review. Int J Mol Sci. 2021;23(1):180. Amabebe E, Anumba DO. Female gut and genital tract microbiota-induced crosstalk and differential effects of short-chain fatty acids on immune sequelae. Front Immunol. 2020;11:2184. Poutahidis T, et al. Pathogenic intestinal bacteria enhance prostate cancer development via systemic activation of immune cells in mice. PLoS ONE. 2013;8(8):e73933. Gootenberg DB, Mitchell CM, Kwon DS. Cervicovaginal microbiota and reproductive health: the virtue of simplicity. Cell Host Microbe. 2018;23(2):159–68. Reynoso-García J, et al. A complete guide to human microbiomes: body niches, transmission, development, dysbiosis, and restoration. Front Syst Biol. 2022;2:951403. Smith SB, Ravel J. The vaginal microbiota, host defence and reproductive physiology. J Physiol. 2017;595(2):451–63. Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe. 2011;10(4):324–35. Lehtoranta L, et al. Healthy vaginal microbiota and influence of probiotics across the female life span. Front Microbiol. 2022;13:819958. Poutahidis T, et al. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin. PLoS ONE. 2013;8(10):e78898. Wang N, et al. The effects of microbiota on reproductive health: a review. Crit Rev Food Sci Nutr. 2024;64(6):1486–507. Fu X, et al. Di-(2‐ethylhexyl) phthalate exposure induces female reproductive toxicity and alters the intestinal microbiota community structure and fecal metabolite profile in mice. Environ Toxicol. 2021;36(6):1226–42. Ervin SM, et al. Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. J Biol Chem. 2019;294(49):18586–99. Fabozzi G, et al. Endocrine-disrupting chemicals, gut microbiota, and human (In) fertility—it is time to consider the triad. Cells. 2022;11(21):3335. Martinez-Guryn K, et al. Small intestine microbiota regulate host digestive and absorptive adaptive responses to dietary lipids. Cell Host Microbe. 2018;23(4):458–69. e5. Wu J, et al. Association between premature ovarian insufficiency and gut microbiota. BMC Pregnancy Childbirth. 2021;21(1):418. Mancini A, et al. Oxidative stress and low-grade inflammation in polycystic ovary syndrome: controversies and new insights. Int J Mol Sci. 2021;22(4):1667. Jiang I, et al. Intricate connections between the microbiota and endometriosis. Int J Mol Sci. 2021;22(11):5644. Singh S, et al. Inflammation in female reproductive health: Double-Edged Sword. In: Tripathi A, Dwivedi A, Gupta S, Poojan S, editors. Inflammation resolution and chronic diseases. Springer, Singapore. p. 143–57. Guo J, et al. Gut microbiota in patients with polycystic ovary syndrome: a systematic review. Reproductive Sci. 2022;29(1):69–83. https://doi.org/10.1007/s43032-020-00430-0. Benner M, et al. How uterine microbiota might be responsible for a receptive, fertile endometrium. Hum Reprod Update. 2018;24(4):393–415. Ishimwe JA, et al. Altered gut microbiome linked to short chain fatty acids production in a rat model of superimposed preeclampsia. FASEB J. 2020;34(S1):1–1. Jin J, et al. Gut dysbiosis promotes preeclampsia by regulating macrophages and trophoblasts. Circ Res. 2022;131(6):492–506. Hasain Z, et al. Gut microbiota and gestational diabetes mellitus: a review of host-gut microbiota interactions and their therapeutic potential. Front Cell Infect Microbiol. 2020;10:188. Gohir W, et al. High-fat diet intake modulates maternal intestinal adaptations to pregnancy and results in placental hypoxia, as well as altered fetal gut barrier proteins and immune markers. J Physiol. 2019;597(12):3029–51. Aldunate M, et al. Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis. Front Physiol. 2015;6:164. Mirmonsef P, et al. Short-chain fatty acids induce pro‐inflammatory cytokine production alone and in combination with toll‐like receptor ligands. Am J Reprod Immunol. 2012;67(5):391–400. Samartzis EP, et al. The expression of histone deacetylase 1, but not other class I histone deacetylases, is significantly increased in endometriosis. Reproductive Sci. 2013;20(12):1416–22. Schilderink R, et al. The SCFA butyrate stimulates the epithelial production of retinoic acid via Inhibition of epithelial HDAC. Am J Physiology-Gastrointestinal Liver Physiol. 2016;310(11):G1138–46. Mirzaei R, et al. Role of microbiota-derived short-chain fatty acids in cancer development and prevention. Biomed Pharmacother. 2021;139:111619. Wang Z, et al. Altered diversity and composition of the gut Microbiome in patients with cervical cancer. Amb Express. 2019;9:1–9. Matsuya-Ogawa M, et al. Oncoprotective effects of short-chain fatty acids on uterine cervical neoplasia. Nutr Cancer. 2019;71(2):312–9. Torres PJ, et al. Gut microbial diversity in women with polycystic ovary syndrome correlates with hyperandrogenism. J Clin Endocrinol Metab. 2018;103(4):1502–11. Gupta M, et al. Expression and localization of Ghrelin and its receptor in ovarian follicles during different stages of development and the modulatory effect of Ghrelin on granulosa cells function in Buffalo. Gen Comp Endocrinol. 2015;210:87–95. Zhao Y, et al. Alginate oligosaccharides improve germ cell development and testicular microenvironment to rescue Busulfan disrupted spermatogenesis. Theranostics. 2020;10(7):3308. Lv S, et al. Gut microbiota is involved in male reproductive function: a review. Front Microbiol. 2024;15:1371667. Xia W, et al. Disruption of Sertoli-germ cell adhesion function in the seminiferous epithelium of the rat testis can be limited to adherens junctions without affecting the blood–testis barrier integrity: an in vivo study using an androgen suppression model. J Cell Physiol. 2005;205(1):141–57. Palladino MA, et al. Effects of lipopolysaccharide-induced inflammation on hypoxia and inflammatory gene expression pathways of the rat testis. Basic Clin Androl. 2018;28:1–12. Tremellen K, et al. Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age. Am J Physiology-Endocrinology Metabolism. 2018;314(3):E206–13. Al-Asmakh M, et al. The gut microbiota and developmental programming of the testis in mice. PLoS ONE. 2014;9(8):e103809. Colldén H, et al. The gut microbiota is a major regulator of androgen metabolism in intestinal contents. Am J Physiology-Endocrinology Metabolism. 2019;317(6):E1182–92. Bélanger A, et al. Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol Metab. 2003;14(10):473–9. Ridlon JM, et al. Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens. J Lipid Res. 2013;54(9):2437–49. Zou H, et al. Testis–gut-reproduction axis: the key to reproductive health. Andrologia. 2024;2024(1):5020917. Smith KB, et al. Pubertal immune challenge suppresses the hypothalamic-pituitary-gonadal axis in male and female mice. Brain Res Bull. 2021;170:90–7. Daniel J, et al. Endotoxin inhibition of luteinizing hormone in sheep. Domest Anim Endocrinol. 2003;25(1):13–9. Shen P, et al. LPS-induced systemic inflammation caused mPOA-FSH/LH disturbance and impaired testicular function. Front Endocrinol. 2022;13:886085. Arroyo P, et al. Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome. PLoS ONE. 2019;14(9):e0223274. Qiao Y, et al. Gut microbiota composition may be an indicator of erectile dysfunction. Microb Biotechnol. 2024;17(1):e14403. Su Q, et al. Specific gut microbiota may increase the risk of erectile dysfunction: a two-sample Mendelian randomization study. Front Endocrinol. 2023;14:1216746. Okamoto T, et al. The association between gut microbiome and erectile dysfunction: a community-based cross-sectional study in Japan. Int Urol Nephrol. 2020;52:1421–8. Su Q, et al. Advances in the study of the relationship between gut microbiota and erectile dysfunction. Sex Med Reviews. 2024;12(4):664–9. https://doi.org/10.1093/sxmrev/qeae049. Zhu Y, et al. Catalpol ameliorates diabetes-induced testicular injury and modulates gut microbiota. Life Sci. 2021;267:118881. Moreira BP, et al. Insights into leptin signaling and male reproductive health: the missing link between overweight and subfertility? Biochem J. 2018;475(22):3535–60. Zhao S, et al. Testicular defense systems: immune privilege and innate immunity. Cell Mol Immunol. 2014;11(5):428–37. Sonnex C. Toll-like receptors and genital tract infection. Int J STD AIDS. 2010;21(3):153–7. Zou H, et al. Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study. Front Endocrinol. 2024;15:1368334. Woo V, Alenghat T. Epigenetic regulation by gut microbiota. Gut Microbes. 2022;14(1):2022407. Besong E, et al. Sodium acetate abates lead-induced sexual dysfunction by upregulating testosterone-dependent eNOS/NO/cGMP signaling and activating Nrf2/HO-1 in male Wistar rat. Volume 397. Naunyn Schmiedeberg’s Arch of Pharmacol; 2024. pp. 1233–43. 2. Lopez-Siles M, et al. Mucosa-associated Faecalibacterium prausnitzii and Escherichia coli co-abundance can distinguish irritable bowel syndrome and inflammatory bowel disease phenotypes. Int J Med Microbiol. 2014;304(3–4):464–75. Salian SR, et al. Supplementation of biotin to sperm preparation medium enhances fertilizing ability of spermatozoa and improves preimplantation embryo development. J Assist Reprod Genet. 2019;36:255–66. Cai H, et al. Gut microbiota supports male reproduction via nutrition, immunity, and signaling. Front Microbiol. 2022;13:977574. Hashem NM, Gonzalez-Bulnes A. The use of probiotics for management and improvement of reproductive eubiosis and function. Nutrients. 2022;14(4):902. Ekgren J, et al. Comparison of tinidazole given as a single dose and on 2 consecutive days for the treatment of nonspecific bacterial vaginosis. Gynecol Obstet Invest. 1988;26(4):313–7. Löfmark S, Edlund C, Nord CE. Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin Infect Dis. 2010;50(Supplement1):S16–23. Petrina MA, et al. Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin. Anaerobe. 2017;47:115–9. Bradshaw CS, Sobel JD. Current treatment of bacterial vaginosis—limitations and need for innovation. J Infect Dis. 2016;214(suppl1):S14–20. Wu S, et al. The right bug in the right place: opportunities for bacterial vaginosis treatment. NPJ Biofilms Microbiomes. 2022;8(1):34. Sirtori CR. The pharmacology of statins. Pharmacol Res. 2014;88:3–11. Badawy A, Elnashar A. Treatment options for polycystic ovary syndrome. Int J Women’s Health. 2011;8:25–35. https://doi.org/10.2147/IJWH.S11304 Hwu Y, et al. Ultra-short Metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2005;90(1):39–43. Rajabi A, et al. An overview of the physiopathology and various treatment strategies for polycystic ovary syndrome. Reproductive Dev Med. 2024;8(01):50–60. Marangoni A, et al. New insights into vaginal environment during pregnancy: a multi-omics approach. Front Mol Biosci. 2021;8:656844. Javed A, Parvaiz F, Manzoor S. Bacterial vaginosis: an insight into the prevalence, alternative treatments regimen and it’s associated resistance patterns. Microb Pathog. 2019;127:21–30. Vodstrcil LA, et al. Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment. BMC Med. 2021;19:1–12. Macklaim JM, et al. Changes in vaginal microbiota following antimicrobial and probiotic therapy. Microb Ecol Health Disease. 2015;26(1):27799. Gholiof M, Adamson-De E, Luca, Wessels JM. The female reproductive tract microbiotas, inflammation, and gynecological conditions. Front Reproductive Health. 2022;4:963752. Shahmirzadi AS, et al. Effect of medicago sativa seed powder (Plus vitamin E vs. vitamin E alone) on semen analysis in men with idiopathic infertility: a double blind randomized clinical trial. J Ethnopharmacol. 2024;322:117606. Ghewade P et al. Role of dietary antioxidant supplements in male infertility: A review. Cureus, 2024;16(6). https://doi.org/10.7759/cureus.61951 Heidarpour M, et al. Comparative effectiveness of antidiabetic drugs as an additional therapy to Metformin in women with polycystic ovary syndrome: A systematic review of metabolic approaches. Int J Endocrinol. 2024;2024(1):9900213. Nahid S, et al. Ovarian hyperstimulation syndrome. In: Shaikh N, Ummunnisa F, Amara UE, editors. Updates in intensive care of OBGY patients. Springer, Singapore; 2024. p. 181–208. Wu L-Y, et al. The role of probiotics in women’s health: an update narrative review. Taiwan J Obstet Gynecol. 2024;63(1):29–36. Vidhate P. Lactobacillus as probiotics: opportunities and challenges for potential benefits in female reproductive health. Am J Transl Res. 2024;16(3):720. Hill C, et al. Expert consensus document: the international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol; 2014. Sheldon IM, et al. Innate immunity and inflammation of the bovine female reproductive tract in health and disease. Reproduction. 2014;148(3):R41–51. López-Moreno A, Aguilera M. Probiotics dietary supplementation for modulating endocrine and fertility microbiota dysbiosis. Nutrients. 2020;12(3):757. Marcone V, Calzolari E, Bertini M. Effectiveness of vaginal administration of Lactobacillus rhamnosus following conventional metronidazole therapy: how to lower the rate of bacterial vaginosis recurrences. New Microbiol. 2008;31(3):429. Barthow C, et al. The probiotics in pregnancy study (PiP study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy. BMC Pregnancy Childbirth. 2016;16:1–14. Zuccotti G, et al. Probiotics for prevention of atopic diseases in infants: systematic review and meta-analysis. Allergy. 2015;70(11):1356–71. Szydłowska I, et al. Effects of probiotics supplementation on the hormone and body mass index in perimenopausal and postmenopausal women using the standardized diet. A 5-week double-blind, placebo-controlled, and randomized clinical study. Volume 25. European Review for Medical & Pharmacological Sciences; 2021. 10. Rautava S, et al. Probiotics modulate host-microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebo-controlled trial. Neonatology. 2012;102(3):178–84. Brantsæter AL, et al. Intake of probiotic food and risk of preeclampsia in primiparous women: the Norwegian mother and child cohort study. Am J Epidemiol. 2011;174(7):807–15. Gu X, et al. Effects of isomaltooligosaccharide and Bacillus supplementation on Sow performance, serum metabolites, and serum and placental oxidative status. Anim Reprod Sci. 2019;207:52–60. Zhang J, et al. Probiotic bifidobacterium lactis V9 regulates the secretion of sex hormones in polycystic ovary syndrome patients through the gut-brain axis. Msystems. 2019;4(2):00017–19. https://doi.org/10.1128/msystems. Molina NM, et al. New opportunities for endometrial health by modifying uterine microbial composition: present or future? Biomolecules. 2020;10(4):593. Chenoll E, et al. Selection of new probiotics for endometrial health. Front Cell Infect Microbiol. 2019;9:114. Itoh H, et al. Lactobacillus gasseri OLL2809 inhibits development of ectopic endometrial cell in peritoneal cavity via activation of NK cells in a murine endometriosis model. Cytotechnology. 2011;63:205–10. Jafarnejad S, et al. Effects of a multispecies probiotic mixture on glycemic control and inflammatory status in women with gestational diabetes: a randomized controlled clinical trial. J Nutr Metabolism. 2016;2016(1):5190846. Zhao S, et al. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in Chow diet-fed mice. J Mol Endocrinol. 2017;58(1):1–14. Younis N, Mahasneh A. Probiotics and the envisaged role in treating human infertility. Middle East Fertil Soc J. 2020;25:1–9. Dardmeh F, et al. Lactobacillus rhamnosus PB01 (DSM 14870) supplementation affects markers of sperm kinematic parameters in a diet-induced obesity mice model. PLoS ONE. 2017;12(10):e0185964. Valcarce D, et al. Probiotic administration improves sperm quality in asthenozoospermic human donors. Benef Microbes. 2017;8(2):193–206. Poutahidis T, et al. Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging mice. PLoS ONE. 2014;9(1):e84877. Ivanov II, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139(3):485–98. Macpherson AJ, et al. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science. 2000;288(5474):2222–6. Hand TW, et al. Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses. Science. 2012;337(6101):1553–6. Celebioglu HU. Effects of potential synbiotic interaction between Lactobacillus rhamnosus GG and Salicylic acid on human colon and prostate cancer cells. Arch Microbiol. 2021;203(3):1221–9. Gibson GR, 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(8):491–502. Artym J, Zimecki M. Antimicrobial and prebiotic activity of lactoferrin in the female reproductive tract: a comprehensive review. Biomedicines. 2021;9(12):1940. Guarner F, et al. World gastroenterology organisation global guidelines: probiotics and prebiotics october 2011. J Clin Gastroenterol. 2012;46(6):468–81. Coppa G, et al. Prebiotics in human milk: a review. Dig Liver Disease. 2006;38:S291–4. Rodrigues LE, et al. Prebiotics mannan-oligosaccharides accelerate sexual maturity in rats: A randomized preclinical study. Veterinary World. 2021;14(5):1210. Brück WM, et al. Effects of bovine α-lactalbumin and casein glycomacropeptide–enriched infant formulae on faecal microbiota in healthy term infants. J Pediatr Gastroenterol Nutr. 2006;43(5):673–9. Mehmood Khan F, et al. The applications of animal models in phage therapy: an update. Human Vaccines & Immunotherapeutics . 2023; 19(1):2175519. Górski A, et al. Phage therapy: combating infections with potential for evolving from merely a treatment for complications to targeting diseases. Front Microbiol. 2016;7:1515. Pal N et al. Phage therapy: an alternative treatment modality for MDR bacterial infections. Infectious Diseases. 2024; pp. 1–33. Lindheim L, 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(1):e0168390. Koren O, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150(3):470–80. Wu D, et al. Cross-talk between gut microbiota and adipose tissues in obesity and related metabolic diseases. Front Endocrinol. 2022;13:908868. Kaltsas A, et al. Microbial dysbiosis and male infertility: understanding the impact and exploring therapeutic interventions. J Pers Med. 2023;13(10):1491. Melo LD, et al. Development of a phage cocktail to control Proteus mirabilis catheter-associated urinary tract infections. Front Microbiol. 2016;7:1024. Letkiewicz S, et al. The perspectives of the application of phage therapy in chronic bacterial prostatitis. FEMS Immunol Med Microbiol. 2010;60(2):99–112. Frazier TH, DiBaise JK, McClain CJ. Gut microbiota, intestinal permeability, obesity-induced inflammation, and liver injury. J Parenter Enteral Nutr. 2011;35:S14–20. Hyman P, Abedon ST. Bacteriophage host range and bacterial resistance. Adv Appl Microbiol. 2010;70:217–48. Wang J-W, et al. Fecal microbiota transplantation: review and update. J Formos Med Assoc. 2019;118:S23–31. Zhang P, et al. Improvement in sperm quality and spermatogenesis following faecal microbiota transplantation from alginate oligosaccharide dosed mice. Gut. 2021;70(1):222–5. Zhao Q, et al. Polyamine metabolism links gut microbiota and testicular dysfunction. Microbiome. 2021;9:1–18. Zhang C, et al. Rescue of male fertility following faecal microbiota transplantation from alginate oligosaccharide-dosed mice. Gut. 2021;70(11):2213–5. Wang M-Y, Sang L-X, Sun S-Y. Gut microbiota and female health. World J Gastroenterol. 2024;30(12):1655. Borin JM, et al. Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice. Gut Microbes. 2023;15(1):2236750. Hsu BB, et al. Dynamic modulation of the gut microbiota and metabolome by bacteriophages in a mouse model. Cell Host Microbe. 2019;25(6):803–14. e5. Draper LA, et al. Autochthonous faecal viral transfer (FVT) impacts the murine Microbiome after antibiotic perturbation. BMC Biol. 2020;18:1–14. Funding This research received no external funding. Author information Authors and Affiliations Contributions Conceptualization, M.K and S.S; writing and original draft preparation, MK (Mona) and SS.; review and editing, PS, NP, DKS, V V, visualization RRT, M.K.; all authors have read and agreed to the published version of the manuscript. Corresponding author Ethics declarations Institutional Review Board Statement NA. Informed Consent Statement: NA. Conflict of interest The authors declare no conflicts of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Singh, S., Kriti, M., Sharma, P. et al. From Gut to Reproductive Health: Exploring Microbiome Interactions and Future Interventions. Reprod. Sci. 32, 3816–3832 (2025). https://doi.org/10.1007/s43032-025-02001-7 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-025-02001-7