The interplay of microbiome, molecular mechanisms, and fertility -an integrated review

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Abstract

The human microbiome, particularly the gut and reproductive tract microbiota, plays a critical role in regulating fertility through complex molecular and immunological mechanisms. This review synthesizes emerging evidence on the bidirectional communication along the gut-reproductive axis, emphasizing how microbial-derived metabolites, such as short-chain fatty acids (butyrate), bile acids, and indoles, modulate systemic inflammation, immune tolerance, hormone metabolism, and energy homeostasis. Dysbiosis, or microbial imbalance, is strongly associated with a range of reproductive pathologies, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, impaired spermatogenesis, and recurrent implantation failure. Furthermore, site-specific microbiomes, such as Lactobacillus-dominated vaginal and uterine communities, are vital for successful implantation and pregnancy maintenance. External factors including diet, environmental toxins, and antibiotic use can disrupt these microbial ecosystems, whereas interventions like probiotics like Lactobacillus and Clostridium butyricum, prebiotics, postbiotics, and fecal microbiota transplantation offer promising avenues for restoring microbial and reproductive health. However, translational challenges remain, including methodological heterogeneity in microbiome research and the need to establish causal mechanisms beyond correlation. Future efforts should prioritize multi-omics integration, randomized controlled trials, and personalized microbiome-based diagnostics and therapeutics to effectively address infertility.
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Abstract

The human microbiome, particularly the gut and reproductive tract microbiota, plays a critical role in regulating fertility through complex molecular and immunological mechanisms. This review synthesizes emerging evidence on the bidirectional communication along the gut-reproductive axis, emphasizing how microbial-derived metabolites, such as short-chain fatty acids (butyrate), bile acids, and indoles, modulate systemic inflammation, immune tolerance, hormone metabolism, and energy homeostasis. Dysbiosis, or microbial imbalance, is strongly associated with a range of reproductive pathologies, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, impaired spermatogenesis, and recurrent implantation failure. Furthermore, site-specific microbiomes, such as Lactobacillus-dominated vaginal and uterine communities, are vital for successful implantation and pregnancy maintenance. External factors including diet, environmental toxins, and antibiotic use can disrupt these microbial ecosystems, whereas interventions like probiotics like Lactobacillus and Clostridium butyricum, prebiotics, postbiotics, and fecal microbiota transplantation offer promising avenues for restoring microbial and reproductive health. However, translational challenges remain, including methodological heterogeneity in microbiome research and the need to establish causal mechanisms beyond correlation. Future efforts should prioritize multi-omics integration, randomized controlled trials, and personalized microbiome-based diagnostics and therapeutics to effectively address infertility. Similar content being viewed by others Data availability Not applicable.

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Figures were created in https://BioRender.com. Funding Postdoctoral funding of Heilongjiang Province (LBH-Z21218). Author information Authors and Affiliations Contributions Xiaoyu Zhang wrote the manuscript; Chaofan Li, Xiaoling Feng, and Xingxing Yuan proofread the manuscript. Corresponding author Ethics declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Clinical trial number Not applicable. 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 Zhang, X., Li, C., Feng, X. et al. The interplay of microbiome, molecular mechanisms, and fertility -an integrated review. Folia Microbiol (2025). https://doi.org/10.1007/s12223-025-01404-y Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s12223-025-01404-y

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