Gut Microbiome Linked to Male Reproductive Disorders

In recent years, with the development of life sciences, more and more attention has been paid to the influence of intestinal flora on the human body. Its functions include synthesizing a variety of essential vitamins, decomposing proteins to generate amino acids, and participating in carbohydrate metabolism. The normal intestinal flora plays an important role in maintaining the health of the body, but some internal and external factors can affect it, disrupt its relative balance, and lead to a series of diseases.

Nowadays, more and more studies have shown that intestinal flora is closely related to the occurrence and development of reproductive system diseases. In addition to common female reproductive system diseases, male reproductive system diseases have gradually attracted the attention of researchers. Moreover, current studies have shown that male reproductive system diseases are related to intestinal flora.

1. Gut flora and semen quality

Studies have shown a strong correlation between enteral protein nutrition and reproduction [1]. In addition to being a staple nutrient in the diet, amino acids are signaling molecules that regulate a variety of physiological processes ranging from spermatogenesis and egg fertilization to embryo implantation. A study of the effects of fecal bacteria on semen suggests that gut bacteria may have an effect on semen. Phaseoloidin, entadamide A, and entadamide A-β-D-glucopyranoside present in the intestinal flora can be hydrolyzed into their respective aglycones, which are all components in semen. Phaseoloidin and entadamide A have anti-complement activity, and phaseoloidin and entadamide A-β-D-glucopyranoside can be metabolized by intestinal flora. Therefore, their anti-complement activity depends on the metabolic level of intestinal bacteria, but the specific mechanism still needs further research to prove.

2. Gut flora and diabetic erectile dysfunction

Studies have confirmed the relationship between gut microbiota and type 2 diabetic erectile dysfunction (T2 DED) , and gut microbiota may be inhibited in T2DED rat model. The relative abundance of beneficial bacteria decreased and that of opportunistic pathogenic bacteria increased. And this change in the bioflora may lead to inflammation that contributes to erectile dysfunction.

3. High-fat diet changes intestinal flora and affects semen quality

In the study, adult male mice were divided into a control group and a 4-week high-fat diet (HFD) group, after which semen and fecal samples were collected. The content of Rikenellaceae in the fecal samples of mice in the HFD group was higher, and the contents of Acinetobacter johnsonii, Streptophyta, Ammoniphilus spp, Bacillus spp and Propionibacterium acnes were less, proving that a high-fat diet can change the microbiota of semen through the intestinal tract, thereby affecting the quality of semen. However, the specific mechanism is still unclear and needs further research and discussion.

Recently, the team of Zhao Zijian, Li Fanghong and Chen Hao from Guangdong University of Technology, and the team of Yao Bing from Nanjing Medical University jointly led the research combined with mouse fecal bacteria transplantation and comprehensive analysis of clinical samples, revealing that high-fat diet damages male reproductive health. Mechanisms of gut microbiota. Results of fecal microbiota transplantation showed that a high-fat diet was associated with reduced sperm count and motility, with the two main associated genera being Bacteroides and Prevotella, and these associations were also confirmed in clinical samples. At the same time, recipient mice had increased intestinal permeability and increased testicular inflammatory factors after receiving the flora of HFD-fed mice. Therefore, the article infers that endotoxin and testicular inflammation may be related to flora-mediated spermatogenesis disorders. This is one of the pioneer articles on microbiome and reproductive health, which may provide new treatment ideas for male infertility.

4. Possible benefits of probiotic supplementation on male fertility

Another study evaluated the role of Lactobacillus plantarum TW1-1 in the testicular injury model of adult male mice induced by diethylhexyl phthalate (DEHP)[4], and it is believed that oral administration of Lactobacillus plantarum TW1-1 can Significantly increased serum testosterone concentrations in DEHP-exposed mice.

Therefore, by supplementing the correct probiotic strains and highly active probiotics, the growth of intestinal epithelial cells and the state of intestinal mucosa can be promoted, and the attachment and growth of harmful bacteria in the intestinal wall can be inhibited, thereby improving the body's immunity and reducing intestinal leakage and other problems, and can improve semen quality and male fertility. On the other hand, probiotics can produce short-chain fatty acids through metabolism, and through the combination with cell surface receptors, enhance the host reproductive hormone levels, such as: testosterone, luteinizing hormone, etc., and ultimately help restore male reproductive health.

Researchers believe the bacteria located in the gastrointestinal tract may be inherited from father to offspring determining later disease risk, such as obesity.  In older males, this bacterium may promote conditions like prostatitis that can result in prostate cancer.

“Microbiomes are influenced by many factors such as temperature, the pH or acidity of the environment and whether there’s a food source to promote bacterial growth,” said Cheryl Rosenfeld, Ph.D., an associate professor of biomedical sciences in the MU College of Veterinary Medicine and an investigator in the Bond Life Sciences Center. “The male reproductive tract includes a unique niche in which bacteria thrive, i.e., the seminal vesicles. These tubular glands produce seminal fluid, and are located in an environment that is temperature controlled and is rich in carbohydrates needed to feed bacteria. Our team set out to isolate this potential microbiome and analyze whether it could harbor harmful bacteria.”

Dr. Rosenfeld and her team, which included Angela Javurek, a former undergraduate researcher in the Bond Life Sciences Center, collected and isolated seminal fluid and vesicles from male mice. The  researchers sequenced the DNA of the bacteria located in the reproductive organs and fluid.

The team then engaged the MU Informatics Research Core Facility (ICRF), a specialized and sophisticated computational biology group to help analyze the data. In Dr. Rosenfeld’s study, Scott Givan, the associate director of the IRCF, and William Spollen, a programmer analyst, employed specialized computer programs that helped narrow and identify the microorganisms.

“The data showed that the bacterial composition found in the male reproductive tract contained potentially detrimental bacteria that can be transmitted to female reproductive partners and offspring,” explained Dr. Rosenfeld. “The bacteria also could be the causative agent of chronic prostatitis, a possible precursor to prostate cancer in males.

“Additionally, further testing showed this bacterial community contains the bacteria that may cause obesity in rats. Understanding how these genetic and environmental factors influence this particular microbiome could help in understanding how possible developmental disorders and diseases are passed down by fathers to their offspring.”

The study, “Discovery of a Novel Seminal Fluid Microbiome and Influence of Estrogen Receptor Alpha Genetic Status,” appears in Scientific Reports, a journal published by Nature.