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

## TL;DR

This review explores how gut and reproductive microbiome imbalances may contribute to male infertility and suggests that probiotics could be a helpful but not standalone treatment.

## Contribution

The paper synthesizes current evidence on the gut–testis axis and proposes a personalized approach to probiotic use in male infertility.

## Key findings

- Dysbiosis in gut, seminal, and urinary microbiomes is linked to impaired semen parameters and inflammation.
- Probiotics or synbiotics may improve semen parameters and reduce oxidative/inflammatory biomarkers in specific infertility cases.
- Personalized treatment strategies are needed, with probiotics considered an adjunct therapy rather than a primary solution.

## 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.