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Dysbiosis of the Gut, Urine, and Semen Microbiomes in Male Infertility
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The authors evaluated rectal, semen, and urine microbiomes in 25 men with primary idiopathic infertility and 12 with proven paternity. Men with infertility demonstrated significant differences in seminal and rectal microbiomes, which also appeared to differ according to the presence of a varicocele or history of vasectomy. Functional alterations in the S-adenosyl-L-methionine cycle were also identified via metagenomic functional metabolic pathway profiling.
- This study identified possible bacterial and functional abnormalities in infertility that may serve as a foundation for future studies aimed at further characterizing these abnormalities and identifying potential therapies.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
Little is known about the role of the genitourinary and gastrointestinal microbiota in the pathogenesis of male infertility.
OBJECTIVE
To compare the taxonomic and functional profiles of the gut, semen, and urine microbiomes of infertile and fertile men.
DESIGN, SETTING, AND PARTICIPANTS
We prospectively enrolled 25 men with primary idiopathic infertility and 12 healthy men with proven paternity, and we collected rectal swabs, semen samples, midstream urine specimens, and experimental controls.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
We performed comprehensive semen analysis, 16S rRNA sequencing for quantitative high-resolution taxonomy, and shotgun metagenomics with a median of 140 million reads per sample for functional metabolic pathway profiling.
RESULTS AND LIMITATIONS
We identified a diverse semen microbiome with modest similarity to the urinary microbiome. Infertile men harbored increased seminal α-diversity and distinct β-diversity, increased seminal Aerococcus, and decreased rectal Anaerococcus. Prevotella abundance was inversely associated with sperm concentration, and Pseudomonas was directly associated with total motile sperm count. Vasectomy appeared to alter the seminal microbiome, suggesting a testicular or epididymal contribution. Anaerobes were highly over-represented in the semen of infertile men with a varicocele, but oxidative stress and leukocytospermia were associated with only subtle differences. Metagenomics data identified significant alterations in the S-adenosyl-L-methionine cycle, which may play a multifaceted role in the pathogenesis of infertility via DNA methylation, oxidative stress, and/or polyamine synthesis.
CONCLUSIONS
This pilot study represents the first comprehensive investigation into the microbiome in male infertility. These findings provide the foundation for future investigations to explore causality and identify novel microbiome-based diagnostics and therapeutics for men with this complex and emotionally devastating disease.
PATIENT SUMMARY
We explored the resident populations of bacteria living in the gut, semen, and urine of infertile and fertile men. We found several important bacterial and metabolic pathway differences with the potential to aid in diagnosing and treating male infertility in the future.
Additional Info
Disclosure statements are available on the authors' profiles:
Functional and Taxonomic Dysbiosis of the Gut, Urine, and Semen Microbiomes in Male Infertility
Eur Urol 2021 Feb 08;[EPub Ahead of Print], SD Lundy, N Sangwan, NV Parekh, MKP Selvam, S Gupta, P McCaffrey, K Bessoff, A Vala, A Agarwal, ES Sabanegh, SC Vij, C EngFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The microbiome has been studied in a wide variety of illnesses and medical conditions, including urologic disorders. The microbiome refers to all bacteria, fungi, and algae, as well as associated agents such as viruses and phages in a specific region (eg, urine, gut, or semen.) The authors of this article observed substantial overlap between seminal and urine microbiomes, and there was also substantial overlap between seminal microbiomes of fertile and infertile males. They did observe differences in specific agents, including Prevotella abundance, which was inversely associated with sperm concentration, and Pseudomonas, which was directly associated with total motile sperm count. As vasectomy altered the seminal microbiome, there is suggestion of a testicular or epididymal contribution. Anaerobes were highly overrepresented in the semen of infertile men with a varicocele. Genomic alterations in the S-adenosyl-L-methionine cycle, which is involved with DNA methylation, oxidative stress, and/or polyamine synthesis, were detected in microbiome changes, which provides a potential pathogenic mechanism for microbiome alterations.
Taken together, what does this mean for infertility patients? This is one of the more comprehensive studies of the “dysbiosis” of semen, urine, and gut microbiome in infertile men. But, despite nearly 10 years of study of microbiome changes in infertility,1 we have very little insight into whether the microbiome is an important area for further investigation or future treatment. Given that treatment with probiotics has not been demonstrated to be effective,2 it appears unlikely that study of the microbiome will be a high-priority target for identifying causes or future treatment for male infertility.
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