Characterisation and comparison of semen microbiota and bacterial load in men with infertility, recurrent miscarriage, or proven fertility

Shahriar Mowla; Linda Farahani; Tharu Tharakan; Rhianna Davies; Goncalo DS Correia; Yun S Lee; Samit Kundu; Shirin Khanjani; Emad Sindi; Raj Rai; Lesley Regan; Dalia Khalifa; Ralf Henkel; Suks Minhas; Waljit S Dhillo; Jara Ben Nagi; Phillip Bennett; David A MacIntyre; Channa N Jayasena

doi:10.7554/elife.96090

Characterisation and comparison of semen microbiota and bacterial load in men with infertility, recurrent miscarriage, or proven fertility

Mowla S, Farahani L, Tharakan T, Davies R, Correia GD, Lee YS, Kundu S, Khanjani S, Sindi E, Rai R, Regan L, Khalifa D, Henkel R, Minhas S, Dhillo WS, Ben Nagi J, Bennett P, MacIntyre DA, Jayasena CN

Published May 8, 2025 eLife, 13

DOI 10.7554/elife.96090 PMC PMC12061474

RRM Academy Synopsis

No single semen bacteria pattern separates fertile from infertile men

Semen bacteria were similar across groups in a one-time study of 223 men. The groups were infertile men, partners of women with recurrent miscarriage, and proven fathers. One unidentified Flavobacterium was linked with abnormal semen quality, even after correction for multiple testing.

Key Findings

The study enrolled 223 men: 63 proven fathers as controls and a study group of 160, including 58 men with male factor infertility and 46 partners of women with recurrent pregnancy loss.
The study group supplied 70 of 82 samples with high sperm DNA fragmentation (85%) and 28 of 33 with elevated reactive oxygen species (ROS) (85%). Oligospermia was also more common there.
Semen bacteria formed three genus-led groups in every study group, led by Streptococcus (23.8% mean relative abundance), Prevotella (24.4%), or Gardnerella and Lactobacillus (35.6% and 35.9%). Species-level clusters were not robust.
Bacterial richness, diversity and load were similar across patient groups. Clusters, richness, diversity and load showed no significant association with semen parameters, sperm DNA fragmentation or ROS.
Flavobacterium genus was associated with abnormal semen quality (q=0.02) and abnormal sperm morphology (q=0.01) after correction. It was present in 36.28% of samples, averaging 1.15% relative abundance where found.

Interpretation

This was a prospective, cross-sectional study that sampled each man once. Among links between specific bacteria and semen measures, only the Flavobacterium result held up after the authors adjusted for many comparisons, and they call it worth further exploration. Flavobacterium lives widely in soil and water, and human infections are rare. The authors report the men had no symptoms of urinary tract infection. They note a single-institution sample with limited ethnic diversity. They call for larger multicenter work to establish causal links.

RRM Context

Restorative reproductive medicine evaluates both partners to find the cause of infertility or pregnancy loss. The authors put the male share at about half of infertility cases. In this cohort, the study group had most samples with high sperm DNA fragmentation or elevated ROS.

Our editorial summary of this paper, not the article's abstract.

Abstract

Several studies have associated seminal microbiota abnormalities with male infertility but have yielded differing results owing to their limited sizes or depths of analyses. The semen microbiota during recurrent pregnancy loss (RPL) has not been investigated. Comprehensively assessing the seminal microbiota in men with reproductive disorders could elucidate its potential role in clinical management. We used semen analysis, terminal-deoxynucleotidyl-transferase-mediated-deoxyuridine-triphosphate-nick-end-labelling, Comet DNA fragmentation, luminol reactive oxidative species (ROS) chemiluminescence, and metataxonomic profiling of semen microbiota by 16S rRNA amplicon sequencing in this prospective, cross-sectional study to investigate composition and bacterial load of seminal bacterial genera and species, semen parameters, ROS, and sperm DNA fragmentation in men with reproductive disorders and proven fathers. 223 men were enrolled, including healthy men with proven paternity (n=63), the male partners in a couple encountering RPL (n=46), men with male factor infertility (n=58), and the male partners of couples with unexplained infertility (n=56). Rates of high sperm DNA fragmentation, elevated ROS, and oligospermia were more prevalent in the study group compared with control. In all groups, semen microbiota clustered into three major genera-dominant groups (1, Streptococcus; 2, Prevotella; 3, Lactobacillus and Gardnerella); no species clusters were identified. Group 2 had the highest microbial richness (p<0.001), alpha-diversity (p<0.001), and bacterial load (p<0.0001). Overall bacterial composition or load has not been found to associate with semen analysis, ROS, or DNA fragmentation. Whilst global perturbation of the seminal microbiota is not associated with male reproductive disorders, men with unidentified seminal Flavobacterium are more likely to have abnormal seminal analysis. Future studies may elucidate if Flavobacterium reduction has therapeutic potential.

Read the guide

Miscarriage and Recurrent Pregnancy Loss: The Workup Most Women Never Get

Miscarriage affects approximately 15% of clinically confirmed pregnancies. Recurrent pregnancy loss (RPL), defined as two or more clinical losses, affects 2 to 5% of couples. Most causes are diagnosable and treatable. This guide covers what the standard workup misses, what RRM-trained clinicians evaluate, and what outcomes look like after cause-based treatment.

22 min read

Topics

Male Fertility › Male Factor Causes › Lifestyle and Environment · Infertility › Recurrent Pregnancy Loss › Immune and Thrombophilia Factors

Shahriar Mowla, Linda Farahani, Tharu Tharakan, Rhianna Davies, Goncalo DS Correia, Yun S Lee, Samit Kundu, Shirin Khanjani, Emad Sindi, Raj Rai, Lesley Regan, Dalia Khalifa, Ralf Henkel, Suks Minhas, Waljit S Dhillo, Jara Ben Nagi, Phillip Bennett, David A MacIntyre, Channa N Jayasena

S Mowla, L Farahani, T Tharakan, R Davies, G Correia, Y Lee, S Kundu, S Khanjani, E Sindi, R Rai, L Regan, D Khalifa, R Henkel, S Minhas, W Dhillo, J Nagi, Phil Bennett, P Bennett, Dave MacIntyre, D MacIntyre, C Jayasena

DOI 10.7554/elife.96090 10.7554/elife.96090 Mowla et al. 2025, Mowla 2025

Characterisation and comparison of semen microbiota and bacterial load in men with infertility, recurrent miscarriage, or proven fertility

No single semen bacteria pattern separates fertile from infertile men

Key Findings

Interpretation

RRM Context

Abstract

Read the guide

Topics

By this author

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