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UCLA Researchers Discover Organisms in Semen Microbiome That Affect Sperm Motility and Male Fertility

Study findings could lead to new clinical laboratory testing biomarkers designed to assess for male infertility

Clinical laboratories are increasingly performing tests that have as their biomarkers the DNA and enzymes found in human microbiota. And microbiologists and epidemiologists know that like other environments within the human body, semen has its own microbiome. Now, a study conducted at the University of California, Los Angeles (UCLA) has found that the health of semen microbiome may be linked to male infertility. 

The UCLA researchers discovered a small group of microorganisms within semen that may impair the sperm’s motility (its ability to swim) and affect fertility.

A total of 73 individuals were included in the study. About half of the subjects were fertile and already had children, while the remaining men were under consultation for fertility issues.

“These are people who have been trying to get pregnant with their partner, and they’ve been unsuccessful,” Sriram Eleswarapu, MD, PhD, a urologist at UCLA and co-author of the study, told Scientific American. “This latter group’s semen samples had a lower sperm count or motility, both of which can contribute to infertility.”

The researchers published their findings in Scientific Reports titled, “Semen Microbiota Are Dramatically Altered in Men with Abnormal Sperm Parameters.”

“There is much more to explore regarding the microbiome and its connection to male infertility,” said Vadim Osadchiy, MD (above), a resident in the Department of Urology at UCLA and lead author of the study, in a UCLA news release. “However, these findings provide valuable insights that can lead us in the right direction for a deeper understanding of this correlation.” Might it also lead to new biomarkers for clinical laboratory testing for male infertility? (Photo copyright: UCLA.)

Genetic Sequencing Used to Identify Bacteria in Semen Microbiome

Most of the microbes present in the semen microbiome originate in the glands of the male upper reproductive tract, including the testes, seminal vesicles and prostate, and contribute various components to semen. “Drifter” bacteria that comes from urine and the urethra can also accumulate in the fluid during ejaculation. Microbes from an individual’s blood, or his partner’s, may also aggregate in semen. It is unknown how these bacteria might affect health.

“I would assume that there are bacteria that are net beneficial, that maybe secrete certain kinds of cytokines or chemicals that improve the fertility milieu for a person, and then there are likely many that have negative side effects,” Eleswarapu told Scientific American.

The scientists used genetic sequencing to identify different bacteria species present within the semen microbiome. They found five species that were common among all the study participants. But men with more of the microbe Lactobacillus iners (L. iners) were likelier to have impaired sperm motility and experience fertility issues.

This discovery was of special interest to the team because L. iners is commonly found in the vaginal microbiome. In females, high levels of L. iners are associated with bacterial vaginosis and have been linked to infertility in women. This is the first study that found a negative association between L. iners and male fertility. 

The researchers plan to investigate specific molecules and proteins contained in the bacteria to find out whether they slow down sperm in a clinical laboratory situation.

“If we can identify how they exert that influence, then we have some drug targets,” Eleswarapu noted.

Targeting Bacteria That Cause Infertility

The team also discovered that three types of bacteria found in the Pseudomonas genus were present in patients who had both normal and abnormal sperm concentrations. Patients with abnormal sperm concentrations had more Pseudomonas fluorescens and Pseudomonas stutzeri and less Pseudomonas putida in their samples.

According to the federal National Institute of Child Health and Human Development (NICHD), “one-third of infertility cases are caused by male reproductive issues, one-third by female reproductive issues, and the remaining one-third by both male and female reproductive issues or unknown factors.” Thus, learning more about how the semen microbiome may be involved in infertility could aid in the development of drugs that target specific bacteria.

“Our research aligns with evidence from smaller studies and will pave the way for future, more comprehensive investigations to unravel the complex relationship between the semen microbiome and fertility,” said urologist Vadim Osadchiy, MD, a resident in the Department of Urology at UCLA and lead author of the study, in a UCLA news release

More research is needed. For example, it’s unclear if there are any links between the health of semen microbiome and other microbiomes that exist in the body, such as the gut microbiome, that cause infertility. Nevertheless, this research could lead to new biomarkers for clinical laboratory testing to help couples who are experiencing fertility issues. 

—JP Schlingman

Related Information:

Semen Microbiome Health May Impact Male Fertility

Semen Microbiota Are Dramatically Altered in Men with Abnormal Sperm Parameters

Semen Has Its Own Microbiome—and It Might Influence Fertility

How Common is Male Infertility, and What Are Its Causes?

Researchers Create Non-stick Coating That Repels External Molecules, Even Viruses and Bacteria; Clinical Laboratories May Soon Find It Easier to Keep Surfaces Free from Bacterial Contamination

Hospital-acquired infections could finally be prevented and no longer threaten the health of patients and hospital workers

In what may be the most significant development in healthcare’s fight against hospital-acquired infections (HAIs), researchers at McMaster University in Hamilton, Ontario, Canada, have developed an ultra-repellent coating that prevents anything—including viruses and bacteria—from adhering to surfaces covered in the material. This fascinating discovery may have great value for both microbiologists and hospital infection control teams, as well as the clinical laboratory and food service industries. 

The self-cleaning material has been proven to repel even the deadliest forms of antibiotic resistant (ABR) superbugs and viruses. This ultimate non-stick coating is a chemically treated form of transparent plastic wrap which can be adhered to surfaces prone to gathering germs, such as door handles, railings, and intravenous therapy (IV) stands.

“We developed the wrap to address the major threat that is posed by multi-drug resistant bacteria,” Leyla Soleymani, PhD, Associate Professor at McMaster University and one of the leaders of the study, told CNN. “Given the limited treatment options for these bugs, it is key to reduce their spread from one person to another.”

The researchers tested their revolutionary coating using two potentially deadly forms of antibiotic-resistant bacteria: Methicillin-resistant staphylococcus aureus (MRSA) and Pseudomonas.

In their study, published in ACS Nano, a journal of the American Chemical Society, titled, “Flexible Hierarchical Wraps Repel Drug-Resistant Gram-Negative and Positive Bacteria,” the researchers stated their material was effective at repelling MRSA 87% of the time and at repelling Pseudomonas 84% of the time. The wrapped surfaces also remained free of Escherichia coli (E. coli) after being exposed to the bacteria.

Bacteria-Resistant Wrap Could Greatly Diminish Threat of Hospital-Acquired Infections

This is a significant breakthrough. Dark Daily has covered the growing danger of hospital-acquired infections in numerous e-briefings, including “Could Proximity of Toilets to Sinks in Medical Intensive Care Units Contribute to Hospital-Acquired Infections?” That report covered research by the Medical College of Wisconsin (MCW) which found that sinks located near toilets in patient rooms were four times more likely to have Klebsiella pneumoniae carbapenemase (KPC)-producing organisms in their drains than sinks that were located farther away from toilets.

According to research published in the peer-reviewed Southern Medical Journal, “KPC-producing bacteria are a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality.”

Were those surfaces covered in this new bacterial-resistant coating, life-threatening infections in hospital ICUs could be prevented.

Taking Inspiration from Nature

In designing their new anti-microbial wrap, McMaster researchers took their inspiration from natural lotus leaves, which are effectively water-resistant and self-cleaning thanks to microscopic wrinkles that repel external molecules. Substances that come in contact with surfaces covered in the new non-stick coating—such as a water, blood, or germs—simply bounce off. They do not adhere to the material.

The “shrink-wrap” is flexible, durable, and inexpensive to manufacture. And, the researchers hope to locate a commercial partner to develop useful applications for their discovery. 

“We’re structurally tuning that plastic,” Soleymani told SciTechDaily. “This material gives us something that can be applied to all kinds of things.”

In the video above, Leyla Soleymani, PhD, Associate Professor at McMaster University, explains how “The new plastic surface—a treated form of conventional transparent wrap—can be shrink-wrapped onto door handles, railings, IV stands, and other surfaces that can be magnets for bacteria such as MRSA and C. difficile. This may be technology that has great value to clinical laboratories and microbiology laboratories. Click here to watch the video. (Image and video copyright: McMaster University/YouTube.)

Industries Outside of Healthcare Also Would Benefit

According to the US Centers for Disease Control and Prevention (CDC), at least 2.8 million people get an antibiotic-resistant infection in the US each year. More than 35,000 people die from these infections, making it one of the biggest health challenges of our time and a threat that needs to be eradicated. This innovative plastic coating could help alleviate these types of infections.

And it’s not just for healthcare. The researchers said the coating could be beneficial to the food industry as well. The plastic surface could help curtail the accidental transfer of bacteria, such as E. coli, Salmonella, and Listeria in food preparation and packaging, according to the published study.

“We can see this technology being used in all kinds of institutional and domestic settings,” Tohid Didar, PhD, Assistant Professor at McMaster University and co-author of the study, told SciTechDaily. “As the world confronts the crisis of anti-microbial resistance, we hope it will become an important part of the anti-bacterial toolbox.”

The research was led by Didar and Soleymani in collaboration with scientists from McMaster’s Institute for Infectious Disease Research (IIDR) and the McMaster-based Canadian Center for Electron Microscopy.

Clinical laboratories also are tasked with preventing the transference of dangerous bacteria to patients and lab personnel. Constant diligence in application of cleaning protocols is key. If this new anti-bacterial shrink wrap becomes widely available, medical laboratory managers and microbiologists will have a new tool to fight bacterial contamination.

—JP Schlingman

Related Information:

Researchers Create Ultimate Non-Stick Coating That Repels Everything—Even Viruses and Bacteria

Flexible Hierarchical Wraps Repel Drug-Resistant Gram-Negative and Positive Bacteria

Scientists Develop Superbug-resistant, Self-cleaning Plastic Wrap

Antibiotic Resistance Threats in the United States

Surface Allows Self-Cleaning

Repel Wraps: Ultimate Non-Stick Coating Repels Everything – Even Viruses and Bacteria

Could Proximity of Toilets to Sinks in Medical Intensive Care Units Contribute to Hospital-Acquired Infections?

Leapfrog Group Report Shows Hospitals Failing to Eliminate Hospital-Acquired Infections; Medical Laboratories Can Help Providers’ Antimicrobial Stewardship Programs

Collaboration between Pathologists, Medical Laboratories, and Hospital Staff Substantially Reduced Hospital-Acquired Infections, AHRQ Reports

University of Edinburgh Study Finds Antimicrobial Bacteria in Hospital Wastewater in Research That Has Implications for Microbiologists

The highly infectious bacteria can survive treatment at local sewage plants and enter the food chain of surrounding populations, the study revealed

Researchers at the University of Edinburgh (UE) in Scotland found large amounts of antimicrobial-resistance (AMR) genes in hospital wastewater. These findings will be of interest to microbiologists and clinical laboratory managers, as the scientists used metagenomics to learn “how abundances of AMR genes in hospital wastewater are related to clinical activity.”

The UE study sheds light on the types of bacteria in wastewater that goes down hospital pipes to sewage treatment plants. The study also revealed that not all infectious agents are killed after passing through waste treatment plants. Some bacteria with antimicrobial (or antibiotic) resistance survive to enter local food sources. 

The scientists concluded that the amount of AMR genes found in hospital wastewater was linked to patients’ length-of-stays and consumption of antimicrobial resistant bacteria while in the hospital.

Using Metagenomics to Surveille Hospital Patients

Antimicrobial resistance is creating super bacteria that are linked to increases in hospital-acquired infections (HAIs) nationwide. Dark Daily has reported many times on the growing danger of deadly antimicrobial resistant “super bugs,” which also have been found in hospital ICUs (see “Potentially Fatal Fungus Invades Hospitals and Public Is Not Informed,” August 26, 2019.)

In a paper the University of Edinburgh published on medRxiv, the researchers wrote: “There was a higher abundance of antimicrobial-resistance genes in the hospital wastewater samples when compared to Seafield community sewage works … Sewage treatment does not completely eradicate antimicrobial-resistance genes and thus antimicrobial-resistance genes can enter the food chain through water and the use of [processed] sewage sludge in agriculture. As hospital wastewater contains inpatient bodily waste, we hypothesized that it could be used as a representation of inpatient community carriage of antimicrobial resistance and as such may be a useful surveillance tool.”

Additionally, they wrote, “Using metagenomics to identify the full range of AMR genes in hospital wastewater could represent a useful surveillance tool to monitor hospital AMR gene outflow and guide environmental policy on AMR.”

AMR bacteria also are being spread by human touch throughout city subways, bus terminals, and mass transportation, making it difficult for the Centers for Disease Control and Prevention (CDC) to identify the source of the outbreak and track and contain it. This has led microbiologists to conduct similar studies using genetic sequencing to identify ways to track pathogens through city infrastructures and transportation systems. (See, “Microbiologists at Weill Cornell Use Next-Generation Gene Sequencing to Map the Microbiome of New York City Subways,” December 13, 2013.)

Antimicrobial stewardship programs are becoming increasingly critical to preventing the spread of AMR bacteria. “By having those programs, [there are] documented cases of decreased antibiotic resistance within organisms causing these infections,” Paul Fey, PhD, of the University of Nebraska Medical Center, told MedPage Today. “This is another indicator of how all hospitals need to implement stewardship programs to have a good handle on decreasing antibiotic use.” [Photo copyright: University of Nebraska.]

Don’t Waste the Wastewater

Antibiotic resistance occurs when bacteria change in response to medications to prevent and treat bacterial infections, according to a World Health Organization (WHO) fact sheet. The CDC estimates that more than 23,000 people die annually from two million antibiotic-resistance infections.

Wastewater, the UE scientists suggest, should not go to waste. It could be leveraged to improve hospitals’ detection of patients with antimicrobial resistance, as well as to boost environment antimicrobial-resistance polices.

They used metagenomics (the study of genetic material relative to environmental samples) to compare the antimicrobial-resistance genes in hospital wastewater against wastewater from community sewage points. 

The UE researchers:

  • First collected samples over a 24-hour period from various areas in a tertiary hospital;
  • They then obtained community sewage samples from various locations around Seafield, Scotland;
  • Finally, they complete the genetic sequencing on an Illumina HiSeq4000 System.

The researchers reported these findings:

  • 181 clinical isolates were identified in the samples of wastewater;
  • 1,047 unique bacterial genes were detected across all samples;
  • 19 genes made up more than 60% of bacteria in samples;
  • Overriding bacteria identified as Pseudomonas and Acinetobacter environmental samples (Pseudomonas fluorescens and Acinetobacter johnsonii) were most likely from hospital pipes;
  • Gut-related bacteria—Faecalibacterium, Bacteroides, Bifidobacterium, and Escherichia, were more prevalent in the hospital samples than in those from the community;
  • Antimicrobial-resistance genes increased with longer length of patient stays, which “likely reflects transmission amongst hospital inpatients,” researchers noted. 

Fey suggests that further research into using sequencing technology to monitor patients is warranted.

“I think that monitoring each patient and sequencing their bowel flora is more likely where we’ll be able to see if there’s a significant carriage of antibiotic-resistant organisms,” Fey told MedPage Today. “In five years or so, sequencing could become so cheap that we could monitor every patient like that.”

Fey was not involved in the University of Edinburgh research.

Given the rate at which AMR bacteria spreads, finding antibiotic-resistance genes in hospital wastewater may not be all that surprising. Still, the University of Edinburgh study could lead to cost-effective ways to test the genes of bacteria, which then could enable researchers to explore different sources of infection and determine how bacteria move through the environment.

And, perhaps most important, the study suggests clinical laboratories have many opportunities to help eliminate infections and slow antibiotic resistance. Microbiologists can help move their organizations forward too, along with infection control colleagues.  

—Donna Marie Pocius

Related Information:

Secrets of the Hospital Underbelly: Abundance of Antimicrobial-Resistance Genes in Hospital Wastewater Reflects Hospital Microbial Use and Inpatient Length of Stay

Antibiotic-Resistance Genes Trouble Hospital Water; Study Emphasizes Importance of Antibiotic Stewardship Programs, Expert Says

Fact Sheet: Antibiotic Resistance

United States Gathers 350 Commitments to Combat Antibiotic Resistance, Action Must Continue

Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenemase Resistance

Dark Daily E-briefings: Hospital-Acquired Infections

NIH Study Reveals Surprising New Source of Antibiotic Resistance that Will Interest Microbiologists and Medical Laboratory Scientists

New Fast, Inexpensive, Mobile Device Accurately Identifies Healthcare-Acquired Infections and Communicates Findings to Doctors’ Smartphones and Portable Computers

Use of these new technologies creates opportunities for clinical laboratories and pathologists to add more value when collaborating with physicians to advance patient care

Ongoing improvements in point-of-care testing are encouraging one major academic medical center to apply this mode of testing to the diagnosis of hospital-acquired infections (HAIs). This development should be of interest to clinical laboratory professionals and pathologists, since it has the potential to create a different way to identify patients with HAIs than medical lab tests done in the central laboratory.

Massachusetts General Hospital (MGH), Harvard Medical School’s (HMS’) largest teaching hospital, has developed a prototype diagnostic system that works with doctors’ smartphones or mobile computers. The hand-held system can identify pathogens responsible for specific healthcare-acquired infections (HAIs) at the point of care within two hours, according to an MGH statement.

The researchers noted that 600,000 patients develop HAIs each year, 10% of which die, and that costs related to HAIs can reach $100 to $150 billion per year. However, as Dark Daily reported, the Centers for Medicare and Medicaid Services (CMS) does not reimburse hospitals for certain HAIs. (See Dark Daily, Consumer Reports Ranks Smaller and Non-Teaching Hospitals Highest in Infection Prevention,” October, 30, 2015.) Thus, the critical need to identify from where the infection originated, which generates a significant proportion of samples tested at the clinical laboratories of the nation’s hospitals and health systems.

Therefore, pathologists and medical laboratory scientists will understand that shifting some of that specimen volume to point-of-care testing will change the overall economics of hospital laboratories.

Smartphone-based Genetic Test for HIAs

The MGH research team created a way to do accurate genetic testing in a simple device powered by a system they call Polarization Anisotropy Diagnostics (PAD). The system measures changes in fluorescence anisotropy through a detection probe’s recognition of bacterial nucleic acid, reported Medscape Medical News. More than 35 probes for detecting bacterial species and virulence factors are available.

Optical test cubes are placed on an electronic base station that transmits data to a smartphone or computer, where results are displayed. “In a pilot clinical test, PAD accuracy was comparable to that of bacterial culture. In contrast to the culture, the PAD assay was fast (under two hours), multiplexed, and cost effective (under $2 per assay), wrote the MGH researchers in the journal Science Advances. (more…)

At the University of Michigan, Research Study Indicates how Composition of Gut Microbiome May Serve as Complementary, Noninvasive Screening Tool for Colon Cancer

If validated by additional research, microbiologists, pathologists, and medical laboratory professionals might soon find analysis of the human microbiome to be a useful marker in screening for colon cancer

Microbiologists may play a greater role in the early detection of colorectal cancer, if the findings of a research study at the University of Michigan (UMich) are confirmed with additional clinical studies.

Combining gut microbiome analysis with traditional risk factors for colorectal cancer—such as body mass index (BMI), age, and race—significantly improved the ability of pathologists to distinguish healthy people from those with precancerous or cancerous lesions, wrote researchers from the UMich in a scholarly paper published in the November 2014 issue in Cancer Prevention Research.

Research findings indicate that gut microbiomes may be a major factor in development of colorectal cancer. However, more research is required to determine if this microbial community has the potential to be clinically useful as screening tool for early-stage disease. (more…)

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