Abstract

Abstract Introduction Approximately 15% of couples struggle with infertility, of which half can be attributed to male factors. Recent advances in next-generation sequencing technologies have augmented our understanding of human health and disease by allowing for accurate and efficient characterization of the human microbiome. A small, albeit growing body of literature suggests a role for the semen microbiome in impacting male fertility and subfertility. Objective Here, we explore the complex relationship between the semen microbiome and alterations of SA parameters. Methods Men presenting for fertility evaluation or men presenting for vasectomy consultation with proven biological paternity were recruited. Clinical data and semen samples were collected from the patients and SA was performed. Patients were then stratified according to alterations in SA parameters. Semen samples underwent DNA extraction, PCR amplification and 16S rRNA sequencing. Taxonomic microbiome community profiling was performed. Results N = 73 participants were included in the study and were stratified based on alterations, or lack thereof, in SA parameters. Men with abnormal sperm motility (N = 27) showed a three-fold higher abundance of Lactobacillus iners (p = 0.0464) compared to those with normal sperm motility (N = 46). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Paraburkholderia phenazinium (p = 0.0247), Pseudomonas fluorescens (p = 0.0101), and Pseudomonas stutzeri (p = 0.0241), but a lower abundance of Pseudomonas putida (p = 0.00478), compared to those with normal sperm concentration (N = 53). Participants with normal SA parameters (N = 40) showed a lower abundance of Peptoniphilus coxii (p = 0.0469) but a higher abundance of Staphylococcus hominis (p = 0.00335) compared to those with any abnormality in sperm concentration or motility (N = 33). These findings are outlined in the differential abundance box plots generated from the Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) in Figure 1 and the canonical correlational analysis visualized in Figure 2. Conclusions Our results suggest that a small group of microorganisms may play a critical role in observed alterations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have been implicated in fertility and subfertility. This is the largest study exploring the relationship between the semen microbiome and abnormalities in SA parameters; our findings provide critical insights that will be important in guiding future, mechanistic investigations. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: MicrogenDx, Metuchen Pharmaceuticals, Antares Pharma, Boston Scientific, and Endo Pharmaceuticals.

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