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

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.