This study represents the largest exploration of the relationship between the semen microbiome and alterations in semen analysis (SA) parameters, namely sperm concentration and motility.2 We recruited 73 participants who presented for either their vasectomy consultation or initial infertility evaluation and stratified them based on alterations in SA parameters.
Our results underscore the rich microbial diversity of semen, which spans the gamut from gram positive microbes like Enterococcus, Corynebacterium, and Lactobacillus spp. to gram negatives like Escherichia and Pseudomonas spp. Remarkably, there were no differences in measures of global diversity, such as alpha- and beta-diversity; however, a small group of microbes emerged as key differentiators in men with normal versus abnormal sperm parameters.
The strongest differentiator was Lactobacillus iners, with a greater than three-fold higher abundance in men with impaired sperm motility. This is not the first time this microbe has been prominently featured in the infertility literature, though this is the first report of an association between L. iners and male factor infertility. A recently published study that included 25 couples undergoing the use of assisted reproductive technologies, found that increased abundance of vaginal lavage L. iners was associated with infertility.3 From a phylogenetic perspective, L. iners represents a particularly intriguing microbe, given its unique ability to synthesize the pro-inflammatory L-lactic acid (compared to the more commonly produced D- isomer),4 along with boasting the smallest genome of any other member of genus Lactobacillus.5
Prior to our work, Lundy et al. published their high-quality investigation of the semen microbiome and male factor infertility, looking at 32 well-phenotyped men. Whereas our results are aligned with theirs in certain respects (microbial richness of semen, etc.) some differences also emerged (differences in global diversity metrics and which particular microbes emerge as differentially more or less abundant).6 Some of these discrepancies can be explained by methodologic and likely geographic differences.
As our understanding of the semen microbiome and male factor fertility matures, we will be able to develop more nuanced hypotheses, with more defined questions beyond the realm of discovery research to ultimately drive microbiota-targeted clinical investigations in the decades to come.
Written by: Vadim Osadchiy, MD, and Sriram V. Eleswarapu, MD, PhD
Division of Andrology, Department of Urology, David Geffen School of Medicine, University of California, Los Angeles
References:
- Osadchiy, V., Mills, J. N., Mayer, E. A. & Eleswarapu, S. V. The seminal microbiome and male factor infertility. Curr. Sex Health Rep. 12, 202–207. (2020).
- Osadchiy, V., Belarmino, A., Kianian, R. et al. Semen microbiota are dramatically altered in men with abnormal sperm parameters. Sci Rep 14, 1068 (2024).
- Campisciano, G. et al. Lactobacillus iners and gasseri, Prevotella bivia, and HPV belong to the microbiological signature negatively affecting human reproduction. Microorganisms. (2020).
- Witkin, S. S. et al. Influence of vaginal bacteria and D- and L-lactic acid isomers on vaginal extracellular matrix metalloproteinase inducer: Implications for protection against upper genital tract infections. mBio (2013).
- Macklaim, J. M., Gloor, G. B., Anukam, K. C., Cribby, S. & Reid, G. At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1. Proc. Natl. Acad. Sci. USA 108(Suppl 1), 4688–4695. (2011).
- Lundy, S. D. et al. Functional and taxonomic Dysbiosis of the gut, urine, and semen microbiomes in male infertility. Eur. Urol. 79, 826–836. (2021).