Dados do Trabalho

Title

Decoding the Microbial Puzzle: The Seminal Microbiome and its Association with Male Infertility

Objective

To summarize the current evidence regarding the seminal microbiome and its association with male infertility and suggest topics that should be addressed by future research to fulfill the existing knowledge gaps.

Methods

We performed a narrative review including all studies published regarding the male tract microbiome in humans published from January 1990 to January 2023. We reviewed studies applying culture-based, polymerase chain reaction (PCR)-based, and next-generation sequencing (NGS)-based approaches to evaluate the seminal microbiome. We extracted data concerning the type of sample (semen or testicular tissue), study design, participants’ characteristics, techniques used, and main findings.

Results

We included 34 studies, comprising 2326 participants. Sixteen studies used culture-based methods, 14 used NGS, and four applied multiple methods to identify microorganisms. No study assessed fungi or viruses. All NGS-based studies identified the presence of bacteria in all semen samples evaluated. Two distinct features of the seminal microbiome were the wide variation of species composition among men and the clustering in microbial communities with a predominant species. The most common genera identified were Lactobacillus, Pseudomonas, Gardnerella, Prevotella, Streptococcus, and Staphylococcus. The genera Lactobacillus was associated with normal semen analysis parameters and asthenozoospermia, whereas the genera Prevotella was consistently linked to poor semen quality. Studies evaluating the testicular microbiome demonstrated that the testicular compartment is not sterile. The phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria were the most frequent in testicular samples. In these lines, despite rigorous antiseptic and aseptic precautions, contamination was responsible for 50–70% of all the detected bacterial reads, suggesting that sperm retrieval procedures are not performed under sterile conditions. The relationship between seminal and vaginal microbiomes has also been investigated. Couples shared 56% of predominant genera, and 61% of the couples with positive cultures in both partners shared at least one genital pathogen. Accordingly, in couples with explained infertility, there was an overlap between the bacterial composition of the seminal and vaginal microbiomes, including increased prevalence of Staphylococcus and Streptococcus genera. The seminal microbiome also impacted reproductive outcomes. Higher counts of Alphaproteobacteria and Gammaproteobacteria in washed sperm and Corynebacterium sp. in raw semen samples were associated with lower embryo quality. In contrast, the mean proportion of the Enterobacteriaceae group in raw semen was higher in couples with improved embryo quality. In addition, bacterial reads were found in the IVF media in 8% of the samples by NGS and in more than 70% by real-time PCR method, with Lactobacillus and Phyllocterium being the most frequent genera. However, bacteria in IVF culture media did not influence the pregnancy rate.

Conclusion

The current literature supports the notion that several genera of bacteria colonize the entirety of the male reproductive tract. These organisms are not living independently. Indeed, they are essential in regulating functions and marinating the hemostasis. Dysbiosis, alterations in the seminal microbiota such as an imbalance in the composition of the microbial community, which includes loss of symbionts, outgrowth of pathobionts or opportunists, and disturbed inter-microbial competition and microbial diversity, may be implicated in the development or worsening of several male infertility conditions. The future directions in understanding the seminal microbiome and its associations with male infertility and semen alterations encompass several crucial areas of investigation. Standardizing protocols, identifying informative variable regions, applying shotgun metagenomics, and addressing contamination concerns are necessary to ensure research findings' reliability and comparability. Longitudinal and prospective studies and investigations into the impacts of infertility causes and commonly prescribed drugs will further our understanding of the seminal microbiota's role in reproductive health.

Keywords

Semen, Bacteria, NGS, Fertility, Dysbiosis