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Microbiome Reveals Clues to Male Infertility

In collaboration with Dr. Eng, Dr. Lundy and colleagues compared the microbiomes of infertile and fertile men and identified several bacterial and metabolic pathway differences that may help diagnose and treat male infertility.


A multidisciplinary research team at Cleveland Clinic has discovered a new aspect of male infertility that may provide future treatment options for couples struggling with infertility. Published in European Urology, the pilot study represents the first comprehensive investigation into the role of the microbiome (the community of microbes existing within specific niches of the body) in male infertility.

“Male infertility causes an incredible amount of stress and anxiety for men,” said lead researcher Scott Lundy, MD, PhD, a urology resident physician at Cleveland Clinic’s Glickman Urological & Kidney Institute and former research fellow in the lab of Charis Eng, MD, PhD, chair of the Genomic Medicine Institute. “We need to remember that when couples are suffering from infertility, nearly half of the time they’re having trouble conceiving due to male factors. And for many of these men, we cannot even give them a reason as to why they’re infertile.”

Partnering with microbiome experts

Despite mounting evidence linking the microbiome to the development of numerous diseases, information on the microbiome’s role in male infertility is lacking. Motivated by this knowledge gap, Dr. Lundy and colleagues decided to investigate whether microbes found in the genitourinary and gastrointestinal tracts are associated with male infertility. 

They approached Dr. Eng about collaborating with her lab’s microbiome team. Dr. Eng’s team studies the microbiome in connection with cancer to identify novel therapeutic and prevention opportunities.

“With the help and mentorship of Dr. Eng, we were able to partner with experts who already understood how to analyze the human microbiome,” said Dr. Lundy.

Analyzing microbiome differences between infertile and fertile men

The team enrolled 25 males with primary idiopathic (spontaneous) infertility and 12 paternity-proven fertile males, from whom they gathered urine samples, rectal swabs and semen samples. They then analyzed the samples using two microbiome research methods: 16S ribosomal RNA marker gene sequencing, which identifies the bacterial species present in a sample; and shotgun metagenomics, which describes the genes and metabolic pathways involved in disease.

“When we investigated the differences in the microbiome between fertile and infertile men, we learned the gut of infertile men included decreased amounts of the bacteria Anaerococcus and increased amounts of Collinsella,” Dr. Lundy explained. “However, semen samples of infertile men contained decreased Collinsella and increased Aerococcus.”

In addition, they found that infertile men had increased expression of the S-adenosyl-L-methionine (SAM) cycle. SAM is a common metabolite that regulates multiple mechanisms critical to the development and maintenance of healthy sperm, which suggests that the SAM cycle may play a multifaceted role in the pathogenesis of infertility.

“It’s not clear whether one or all of these mechanisms play a role in microbiome-mediated male infertility, but this data is nevertheless important and further studies are planned,” noted Dr. Lundy.

The researchers also tested if clinical varicocele, a dilation of the testicular veins associated with infertility, is associated with differences in the seminal microbiome. They compared semen samples of infertile men with or without a clinical varicocele and identified significant differences in pathway expression.

“Our hope moving forward is that this study forms the foundation for future studies of male infertility and men’s health,” said Dr. Lundy. “We hope this research gives a voice to men and couples dealing with infertility and delivers hope that a resolution is possible.”

This study was supported by the Cleveland Clinic Foundation Research Program Committee Grant.

Story adapted from ConsultQD.

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