Probiotics as Microbiome Modulators in Male Infertility: Rethinking Dysbiosis Across the Gut–Testis Axis

Male infertility contributes substantially to couple infertility, and a large proportion of cases remain idiopathic. Dysbiosis within the gut, seminal, and urinary microbiomes has been associated with impaired semen parameters, reproductive tract inflammation, and oxidative stress. This narrative review, informed by a structured literature search, summarizes current evidence for the gut-testis axis and the androbactome in male infertility and discusses mechanistic pathways linking microbial imbalance to sperm dysfunction. Proposed mechanisms include immune activation, increased oxidative stress, endocrine and metabolic perturbations, and disruption of epithelial barriers, including the blood-testis barrier. Early clinical trials report that selected probiotic or synbiotic formulations may be associated with improvements in one or more World Health Organization (WHO) semen parameters and with reductions in oxidative or inflammatory biomarkers (surrogate laboratory endpoints; pregnancy and live-birth outcomes are rarely reported and remain unproven) in selected populations, such as idiopathic infertility and the post-varicocelectomy setting. Given patient heterogeneity, a personalized approach requires prespecified clinical phenotypes and measurable monitoring targets, rather than indiscriminate supplementation. At present, probiotics should be considered an adjunct rather than a stand-alone therapy. Well-designed, contamination-aware microbiome studies and adequately powered randomized trials with clinically meaningful endpoints, including pregnancy and live birth, are required before routine clinical implementation. This synthesis is intended to support personalized counseling and trial design by clarifying candidate phenotypes, appropriate monitoring endpoints, and realistic limitations of current evidence.

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Publication Details

Journal
Journal of Personalized Medicine
Published
2026-02-06
DOI
https://doi.org/10.3390/jpm16020099
Primary Topic
Sperm and Testicular Function
Type
article
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article

Probiotics as Microbiome Modulators in Male Infertility: Rethinking Dysbiosis Across the Gut–Testis Axis

Fotios Dimitriadis, MICHAEL CHRISOFOS, Ilias Giannakodimos, Athanasios Zachariou et al.
Journal of Personalized Medicine
Sperm and Testicular Function
article

Probiotics as Microbiome Modulators in Male Infertility: Rethinking Dysbiosis Across the Gut–Testis Axis

Fotios Dimitriadis, MICHAEL CHRISOFOS, Ilias Giannakodimos, Athanasios Zachariou, Marios Stavropoulos, Spyros Pournaras, Aris Kaltsas, Eleftheria Markou, Nikolaos Sofikitis, Stamatis Papaharitou
article en

Abstract

Male infertility contributes substantially to couple infertility, and a large proportion of cases remain idiopathic. Dysbiosis within the gut, seminal, and urinary microbiomes has been associated with impaired semen parameters, reproductive tract inflammation, and oxidative stress. This narrative review, informed by a structured literature search, summarizes current evidence for the gut-testis axis and the androbactome in male infertility and discusses mechanistic pathways linking microbial imbalance to sperm dysfunction. Proposed mechanisms include immune activation, increased oxidative stress, endocrine and metabolic perturbations, and disruption of epithelial barriers, including the blood-testis barrier. Early clinical trials report that selected probiotic or synbiotic formulations may be associated with improvements in one or more World Health Organization (WHO) semen parameters and with reductions in oxidative or inflammatory biomarkers (surrogate laboratory endpoints; pregnancy and live-birth outcomes are rarely reported and remain unproven) in selected populations, such as idiopathic infertility and the post-varicocelectomy setting. Given patient heterogeneity, a personalized approach requires prespecified clinical phenotypes and measurable monitoring targets, rather than indiscriminate supplementation. At present, probiotics should be considered an adjunct rather than a stand-alone therapy. Well-designed, contamination-aware microbiome studies and adequately powered randomized trials with clinically meaningful endpoints, including pregnancy and live birth, are required before routine clinical implementation. This synthesis is intended to support personalized counseling and trial design by clarifying candidate phenotypes, appropriate monitoring endpoints, and realistic limitations of current evidence.

Journal of Personalized MedicineVol. 16(2)
University of Ioannina (GR), National and Kapodistrian University of Athens (GR), Aristotle University of Thessaloniki (GR), Piraeus Bank (GR), University Hospital of Ioannina (GR)
Openalex Percentile: Top 67%
Sperm and Testicular Function
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