The microbiome of the male reproductive tract: uncovering its composition and origins

Résumé

Almost every part of our body has coevolved microbial community and as more knowledge of the human microbiota (i.e., community of microorganisms) is acquired, it is becoming evident that microorganisms have a significant impact on our health and well-being. However, an imbalance in this host-microbe relationship can lead to a disease. In the context of human reproductive health, the microbiome (i.e., microorganisms and their genomes) of semen is a field of increasing scientific interest, although this microbial niche has received relatively limited attention compared to other body sites. Despite the evidence of seminal microbiome, a few studies have investigated the sources and acquisition pathways of microorganisms present in the semen. Likewise, the complete influence of the microbes of adjacent sites and its association with male fertility remains unclear. Recent studies have shown that semen harbours its own set of microbes which is polymicrobial and for a low biomass. Further, it has been shown that microorganisms in the semen substantially vary between individuals, suggesting that each has its unique and potentially individual bacterial community profile. Also, certain correlations have been established between the presence of specific bacteria in semen and its quality parameters. Further, bacteria are shared among partners and this bidirectional exchange can influence the microbial make-up of either partner with an implication on their health. This Doctoral Thesis studies the origin of the seminal microbial communities. The objectives of this Doctoral Thesis were: 1) to investigate the existence of microbes in human testicular samples; 2) to uncover potential sources and routes of microbial colonisation in the semen, and the effect of sterilisation method of vasectomy on seminal microenvironment; 3) to compile available data of microbial niches within couples, to assess the shared microbes within couple, and to determine the potential impact of female and male reproductive tract microbiomes on couple’s health; and 4) to highlight the methodological considerations and provide recommendations for low biomass microbial studies using endometrium as the study model. Four studies were carried out to address these objectives, with the main findings being: 1) human maturing spermatozoa from testicle biopsies harbour its unique low biomass microbial signature, with a possible role in the functional sperm development, which could be one source of the seminal microbial composition (Study I). 2) We found considerable differences in microbial diversity when comparing pre- and post-vasectomy semen samples which suggest that vasectomy influences the seminal microbial composition. Further, semen shares 50% of bacterial communities with urine, underscoring the intricate relationships between anatomically close but functionally distinct niches (Study II). 3) During unprotected sexual intercourse, the vaginal and seminal microbes mix and influence each other, forming the “seminovaginal microbiota” which influences the species composition of the couple’s reproductive tract, having both beneficial and detrimental effects on the health of couples (Study III). 4) The reproductive microbiome field requires clear, reproducible, and well-controlled study design to elucidate the healthy seminal microbiome. When analysing low microbial biomass tissue (as the testicle and semen), systematic control and elimination of possible contamination is crucial to obtain reliable microbiome data over the host information and to minimise misinterpretation of the results. We have proposed a set of guidelines for conducting microbiome studies on low biomass reproductive sites (Study IV).