Introduction: Infertility, defined as the failure to conceive after 12 months of regular unprotected intercourse, is a pervasive global health challenge affecting an estimated 17.5% of couples. A significant portion of cases are classified as "unexplained," highlighting a critical gap in our understanding of the multifactorial pathophysiology of conception. Beyond the established causes within the reproductive organs themselves, emerging research has unveiled the profound influence of the gut microbiota on systemic host physiology. The "gut-reproductive axis" posits that the composition and metabolic activity of gut bacteria can directly and indirectly influence reproductive function in both men and women. Dysbiosis, an imbalance in this microbial community, is linked to chronic inflammation, hormonal irregularities, and metabolic disorders—all of which are known detractors of fertility. This review investigates this novel axis and explores the potential of targeted probiotic supplementation, using a theoretical "MEKEL Probiotic" formulation as a model, to restore natural microbial and thereby improve reproductive outcomes
Methods: This narrative review was conducted through a systematic search of major scientific databases, including PubMed, Scopus, and Web of Science. The search encompassed articles published from 2000 to 2024 using a combination of keywords and MESH terms such as "infertility," "gut microbiota," "dysbiosis," "probiotics," "ESTROBOLOM," "inflammation," "sperm quality," and "PCOS." The scope included in vitro studies, animal models, and human clinical trials. The primary focus was to synthesize evidence on the mechanisms linking gut health to reproductive function. Based on the identified mechanisms, a theoretical probiotic formulation ("MEKEL Probiotic") was conceptually designed. Its proposed composition was selected by identifying specific bacterial strains with robust clinical evidence for modulating each key pathway (e.g., inflammation, estrogen metabolism, insulin sensitivity, oxidative stress). The efficacy of this proposed formulation is inferred from the aggregate findings of the reviewed studies on individual strains and their documented roles in the gut-reproductive axis.
Results: The synthesis of current literature reveals several robust mechanisms connecting gut health to fertility. Firstly, dysbiosis can compromise intestinal barrier integrity, leading to metabolic endotoxemia (elevated LPS) and a state of systemic inflammation that disrupts Oogenesis, embryogenesis, and implantation. Secondly, the gut microbiota regulates estrogen circulation via the "ESTROBOLOB"; bacterial β-glucuronidase activity directly influences estrogen reabsorption, and dysbiosis can lead to either deficient or excessive estrogen levels, impacting endometrial receptivity and conditions like endometriosis. Thirdly, bacterial metabolites, particularly short-chain fatty acids (SCFAs) like butyrate, enhance insulin sensitivity, which is crucial for mitigating anovulation in conditions like PCOS. In males, specific probiotic strains (e.g., Lactobacillus fermentum, L. REUTERI) demonstrate significant antioxidant properties, reducing seminal reactive oxygen species and improving key semen parameters including concentration, motility, and morphology.
Based on these results, the proposed " MEKEL Probiotic" formulation is theorized to contain a synergistic combination of strains: Lactobacillus RHAMNOSUS and L. acidophilus for gut barrier support and inflammation reduction; Bifidobacterium longum for folate production; L. fermentum and L. REUTERI for antioxidant support in male fertility; and Bifidobacterium breve for SCFA production and ESTROBOLOME modulation. The aggregate data suggest that such a multi-strain, mechanism-targeted approach holds significant promise for addressing the root systemic causes of subfertility
Conclusion: The findings of this review strongly support the existence of a critical gut-reproductive axis, where dysbiosis acts as a key contributor to a suboptimal internal environment for conception. The proposed mechanisms—systemic inflammation, hormonal dysregulation, metabolic dysfunction, and oxidative stress—provide a plausible biological framework to explain how rectifying gut health can positively influence fertility. The theoretical "MEKEL Probiotic" formulation embodies a novel biotechnological approach to infertility, moving beyond symptom management to address underlying systemic dysfunction.
However, while the mechanistic evidence is compelling, most supporting data for probiotics in infertility are preclinical or derived from small-scale human studies. Direct clinical evidence for a specific multi-strain formulation like the one proposed is currently lacking. The field now demands large-scale, randomized, double-blind, placebo-controlled trials (RCTs) to validate the efficacy of targeted probiotic blends. Future research must also focus on standardizing strains and dosages and utilizing omics technologies to personalize probiotic therapy based on an individual's unique microbial signature.
In conclusion, adjuvant probiotic therapy represents a paradigm shift in fertility management. By modulating the gut-reproductive axis, formulations like the proposed "MEKEL Probiotic" offer a safe, non-invasive, and holistic strategy to complement existing assisted reproductive technologies, potentially improving success rates for millions of couples struggling with infertility.
Keywords: Infertility, Gut Microbiota, Probiotics, Dysbiosis, Inflammation,