bacteria Archives

PMA-based PCR amplifies DNA from only live bacteria in urine

February 1, 2022

The question of why urinary tract infection (UTI) symptoms can persist in some patients who have been seemingly appropriately treated with antibiotics and have negative post-antibiotic urine cultures is one that urologists have long sought to answer.

Experts at Children’s National Hospital have successfully developed propidium monoazide (PMA)-based polymerase chain reaction (PCR) methods that amplify DNA from only live bacteria in urine. The study’s results, published in Frontiers, suggest that non-PMA bound DNA from live bacteria can be present in urine, even after antibiotic treatment.

PMA has been shown to differentiate between non-viable and viable bacteria in various settings. However, its effectiveness in urine has not been previously studied.

The question of why urinary tract infection (UTI) symptoms can persist in some patients who have been seemingly appropriately treated with antibiotics and have negative post-antibiotic urine cultures is one that urologists have long sought to answer.

“One theory is that very low levels of bacteria that don’t show up on cultures may be the cause,” says Michael Hsieh, M.D., director of Transitional Urology at Children’s National and senior author of the study.

Although PCR has previously been used to try and confirm this theory, the use of this method has been criticized because PCR can amplify DNA from dead bacteria (which obviously don’t cause UTI).

The authors developed a PCR test that selectively detects DNA from live bacteria. In a preclinical setting, results show that with the use of antibiotics, cultures collected can be negative but urine can contain DNA from live bacteria, as detected using the PCR test.

“We think something similar can occur in patients and we show some data in the paper confirming the PCR test can work with patient samples,” Dr. Hsieh adds. “I’m excited that we might finally have an explanation as to why some patients have persistent UTI symptoms after antibiotic treatment.”

Namely, he adds, that these patients still have a UTI. This may lead to better follow-up management of patients with UTI. The next step is to confirm the theory in patients.

Probiotic use in pediatric medicine

January 14, 2021

Illustration of Bifidobacterium

Probiotics have received significant attention within both the scientific and lay communities for their potential health-promoting properties, including the treatment or prevention of various conditions in children.

In a recent article published by Pediatric Research, Michael Hsieh, M.D., Ph.D., director of Transitional Urology at Children’s National Hospital, and other experts review the published data on use of specific probiotic strains for three common pediatric conditions: the prevention of urinary tract infections and antibiotic-associated diarrhea and the treatment of atopic dermatitis.

Parasite-derived molecule could accelerate recovery from UTI

December 10, 2020

Eggs from S. haematobium may produce the molecule IPSE to reduce the immune response against them, which happens to dampen UTI-induced bladder inflammation.

IPSE, a urogenital parasite-derived immunomodulatory molecule, can suppress bladder pathogenesis and anti-microbial peptide gene expression in bacterial urinary tract infection (UTI) according to a new study led by Michael Hsieh, Ph.D., director of Transitional Urology at Children’s National Hospital.

Half of all girls and women, and about 5% of boys and men, will have at least one urinary tract infection (UTI) in their lifetimes.

“Although antibiotics are very helpful for these infections, there are concerns that overuse of antibiotics may contribute to antibiotic-resistant infections,” Dr. Hsieh said. “There are also concerns that antibiotic therapy for UTI does not uniformly resolve infection-induced or inflammation-associated symptoms quickly.”

Parasitic infections are often associated with bacterial co-infections for unclear reasons. This may be true for urogenital schistosomiasis (caused by Schistosoma haematobium infection) and bacterial urinary tract co-infection (UTI), the study noted. Dr. Hsieh and other leading experts previously reported that this co-infection is facilitated by S. haematobium eggs triggering interleukin-4 (IL-4) production and sought to dissect the underlying mechanisms.

“Despite S. haematobium’s ability to make hosts more susceptible to UTI, we have identified IPSE, a bladder parasite protein, as a potential anti-inflammatory agent to accelerate recovery from UTI,” Dr. Hsieh explained. “S. haematobium eggs may produce IPSE to reduce the immune response against them, which happens to dampen UTI-induced bladder inflammation. It may be possible to develop IPSE as novel therapeutic to accelerate recovery from UTI.”

The study’s data showed that IPSE may play a major role in S. haematobium-associated urinary tract co-infection, although in an unexpected way. The study’s findings also indicated that IPSE either works in concert with other IL-4 -inducing factors to increase susceptibility of S. haematobium-infected hosts to bacterial co-infection or does not contribute to enchaining vulnerability to this co-infection.

You can find the full study published in Parasites and Vectors. Learn more about the Children’s National Department of Urology.

Once overlooked cellular messengers could combat antibiotic resistance

March 18, 2020

Children’s National Hospital researchers for the first time have isolated bacterial extracellular vesicles from the blood of healthy donors. The team theorizes that the solar eclipse lookalikes contain important signaling proteins and chromatin, DNA from the human host.

Children’s National Hospital researchers for the first time have isolated bacterial extracellular vesicles from the blood of healthy donors, a critical step to better understanding the way gut bacteria communicate with the rest of the body via the bloodstream.

For decades, researchers considered circulating bacterial extracellular vesicles as bothersome flotsam to be jettisoned as they sought to tease out how bacteria that reside in the gut whisper messages to the brain.

There is a growing appreciation that extracellular vesicles – particles that cells naturally release – actually facilitate intracellular communication.

“In the past, we thought they were garbage or noise,” says Robert J. Freishtat, M.D., MPH, associate director, Center for Genetic Medicine Research at Children’s National Research Institute. “It turns out what we throw away is not trash.”

Kylie Krohmaly, a graduate student in Dr. Freishtat’s laboratory, has isolated from blood, extracellular vesicles from Escherichia coli and Haemophilus influenzae, common bacteria that colonize the gut, and validated the results via electron microscopy.

“The images are interesting because they look like they have a bit of a halo around them or penumbra,” Krohmaly says.

The team theorizes that the solar eclipse lookalikes contain important signaling proteins and chromatin, DNA from the human host.

“It’s the first time anyone has pulled them out of blood. Detecting them is one thing. Pulling them out is a critical step to understanding the language the microbiome uses as it speaks with its human host,” Dr. Freishtat adds.

Krohmaly’s technique is so promising that the Children’s National team filed a provisional patent.

The Children’s research team has devised a way to gum up the cellular works so that bacteria no longer become antibiotic resistant. Targeted bacteria retain the ability to make antibiotic-resistance RNA, but like a relay runner dropping rather than passing a baton, the bacteria are thwarted from advancing beyond that step. And, because that gene is turned off, the bacteria are newly sensitive to antibiotics – instead of resistant bacteria multiplying like clockwork these bacteria get killed.

“Our plan is to hijack this process in order to turn off antibiotic-resistance genes in bacteria,” Dr. Freishtat says. “Ultimately, if a child who has an ear infection can no longer take amoxicillin, the antibiotic would be given in tandem with the bacteria-derived booster to turn off bacteria’s ability to become antibiotic resistant. This one-two punch could become a novel way of addressing the antibiotic resistance process.”

ISEV2020 Annual Meeting presentation
(Timing may be subject to change due to COVID-19 safety precautions)
Oral with poster session 3: Neurological & ID
Saturday May 23, 2020, 5 p.m. to 5:05 p.m. (ET)
“Detection of bacterial extracellular vesicles in blood from healthy volunteers”
Kylie Krohmaly, lead author; Claire Hoptay, co-author; Andrea Hahn, M.D., MS, infectious disease specialist and co-author; Robert J. Freishtat, M.D., MPH, associate director, Center for Genetic Medicine Research at Children’s National Research Institute and senior author.

Understanding gut bacteria: forces for good (and sometimes evil)

September 11, 2019

In a paper published Sept. 11, 2019, in PLOS ONE, a multi-institutional research team led by George Washington University (GW) faculty found 157 different types of organisms (eight phyla, 18 classes, 23 orders, 38 families, 59 genera and 109 species) living inside the guts of healthy volunteers.

Back in 2015, an interdisciplinary group of research scientists made their case during a business pitch competition: They want to create a subscription-based service, much like 23andMe, through which people could send in samples for detailed analyses. The researchers would crunch that big data fast, using a speedy algorithm, and would send the consumer a detailed report.

But rather than ancestry testing via cheek swab, the team sought to determine the plethora of diverse bacterial species that reside inside an individual’s gut in their ultimate aim to improve public health.

Hiroki Morizono, Ph.D., a member of that team, contributed detailed knowledge of Bacteroides, a key organism amid the diverse array of bacterial species that co-exist with humans, living inside our guts. These symbiotic bacteria convert the food we eat into elements that ensure their well-being as well as ours.

“Trillions of bacteria live in the gut. Bacteroides is one of the major bacterial species,” says Morizono, a principal investigator in the Center for Genetic Medicine Research at Children’s National in Washington, D.C. “In our guts they are usually good citizens. But if they enter our bloodstream, they turn evil; they’re in the wrong place. If you have a bacteroides infection, the mortality rate is 19%, and they resist most antibiotic treatments.”

The starting point for their project – as well as step one for better characterizing the relationship between gut bacteria and human disease – is taking an accurate census count of bacteria residing there.

In a paper published Sept. 11, 2019, in PLOS ONE, a multi-institutional research team led by George Washington University (GW) faculty did just that, finding 157 different types of organisms (eight phyla, 18 classes, 23 orders, 38 families, 59 genera and 109 species) living inside the guts of healthy volunteers.

The study participants were recruited through flyers on the GW Foggy Bottom campus and via emails. They jotted down what they ate and drank daily, including the brand, type and portion size. They complemented that food journal by providing fecal samples from which DNA was extracted. Fifty fecal metagenomics samples randomly selected from the Human Microbiome Project Phase I research were used for comparison purposes.

“The gut microbiome inherently is really, really cool. In the process of gathering this data, we are building a knowledge base. In this paper, we’re saying that by looking at healthy people, we should be able to establish a baseline about what a normal, healthy gut microbiome should look like and how things may change under different conditions,” Morizono adds.

And they picked a really, really cool name for their bacteria abundance profile: GutFeelingKB.

“KB is knowledge base. Our idea, it’s a gut feeling. It’s a bad joke,” he admits. “Drosophila researchers have the best names for their genes. No other biology group can compete. We, at least, tried.”

Next, the team will continue to collect samples to build out their bacteria baseline, associate it with clinical data, and then will start looking at the health implications for patients.

“One thing we could use this for is to understand how the bacterial population in the gut changes after antibiotic treatment. It’s like watching a forest regrow after a massive fire,” he says. “With probiotics, can we do things to encourage the right bacteria to grow?”

In addition to Morizono, study co-authors include Lead Author Charles H. King, and co-authors Hiral Desai, Allison C. Sylvetsky, Jonathan LoTempio, Shant Ayanyan, Jill Carrie, Keith A. Crandall, Brian C. Fochtman, Lusine Gasparyan, Naila Gulzar, Najy Issa, Lopa Mishra, Shuyun Rao, Yao Ren, Vahan Simonyan, Krista Smith and Senior Author, Raja Mazumder, all of George Washington University; Paul Howell and Sharanjit VedBrat, of KamTek Inc.; Konstantinos Krampis, of City University of New York; Joseph R. Pisegna, of VA Greater Los Angeles Healthcare System; and Michael D. Yao, of Washington DC VA Medical Center.

Financial support for research described in this post was provided by the National Science Foundation under award number 1546491 and the National Institutes of Health National Center for Advancing Translational Sciences under award number UL1TR000075.

Critters bugging! Test your infectious disease knowledge

September 10, 2019

Which micro-organisms lurk within urine?

February 11, 2019

Does ZIP code factor into genitourinary system health?

January 18, 2019

Clinicians suspect that taking probiotics, such as lactobacillus supplements, and making changes to diet may prevent urinary diseases that occur commonly among pediatric patients. A research team led by Children’s faculty is exploring whether changes in the built environment also affect the urinary microbiome.

Emerging evidence suggests that the variety and volume of bacteria that reside in the bladder – the urinary microbiome – significantly impact whether people’s genitourinary systems remain healthy or become susceptible to disease.

Already, clinicians suspect that taking probiotics and making changes to diet may prevent urinary diseases that occur commonly among pediatric patients. A research team led by Children’s faculty is exploring whether changes in the built environment also affect the urinary microbiome.

Using experimental models, they looked at how stable the urinary microbiome was over time. Then, they measured the potential effect of changing the built environment on the urinary microbiome of preclinical models.

They did this by following six C57BL/6 experimental models for five months, starting from when they were nine weeks old. They collected urine specimens when the study began and repeated sample collections each month. The multidisciplinary team isolated microbial DNA from these specimens to determine the makeup of the bacterial community present in their urinary tracts.

All of the experimental models shared a single cage, drank the same water and ate the exact same chow. At four months, however, they moved the preclinical models to a different facility within the same county. Their chow and bedding remained unchanged, but the water source changed since they received tap water at both locations.

“There were no changes in the proportion of specific bacteria in the urinary microbiomes from month zero through month five, which means the urinary microbiomes of healthy experimental models remain stable over time,” says Michael Hsieh, M.D., Ph.D., a urologist at Children’s National Health System and senior author of the work presented during the Pediatric Urology Fall Conference. “However, the convergence of the Shannon Diversity Index, the clustering seen on Principal coordinate analyses and changes in functional analyses taken as a whole suggest that an overall shift of the urinary microbiome occurred due to a change in the physical environment.”

This work suggests that where patients live could influence which bacteria grow in the urinary tracts, including during urinary tract infections.

The Societies for Pediatric Urology’s Pediatric Urology Fall Conference

“Effects of time and the built environment on the stability of the mouse urinary microbiome: implications for clinical utility.”

Catherine S. Forster, M.D., MS, pediatric hospitalist, Children’s National; James Cody, Ph.D., Biomedical Research Institute; Nirad Banskota, MS, Biomedical Research Institute; Crystal Stroud, MS, Children’s National; Ljubica Caldovic, Ph.D., principal investigator, Children’s National; and Michael Hsieh, M.D., Ph.D., urologist, Children’s National.

Urinary bacteria in spinal cord injury cases may tip balance toward UTIs

January 17, 2019

Patients with spinal cord injuries nearly universally have bacteria present in their urine regardless of whether they have a urinary tract infection.

The fallout from spinal cord injury doesn’t end with loss of mobility: Patients can have a range of other issues resulting from this complex problem, including loss of bladder control that can lead to urine retention. One of the most serious implications is urinary tract infections (UTIs), the most common cause of repeat hospitalization in people with spinal cord injuries, explains Hans G. Pohl, M.D., associate chief in the division of Urology at Children’s National Health System.

Diagnosing UTIs in people with spinal cord injuries is trickier than in people who are otherwise healthy, Dr. Pohl explains. Patients with spinal cord injuries nearly universally have bacteria present in their urine regardless of whether they have a UTI. It’s unclear whether these bacteria are innocent bystanders or precursors to UTIs in patients who don’t yet show symptoms. And although antibiotics can wipe out this bacterial population, these drugs can have undesirable side effects and frequent use can promote development of antibiotic-resistant bacteria.

Although clinical dogma has long promoted the idea that “healthy” urine is sterile, Dr. Pohl and colleagues have shown that a variety of bacteria live in urine, even in people without symptoms. These microorganisms, like the intestinal microbiome, live in harmony with their hosts and may even help promote health. However, it’s unclear what this urinary microbiome might look like for patients with spinal cord injury before, during and after UTIs.

To start investigating this question, Dr. Pohl and co-authors recently reported a case study they published online Sept. 21, 2018, in Spinal Cord Series and Cases. The case report about a 55-year-old man who had injured the thoracic segment of his spinal cord—about the level of the bottom of his shoulder blades—in a skiing accident when he was 19 was selected as “Editor’s Choice” for the journal’s October 2018 issue. The patient had a neurogenic bladder, which doesn’t function normally due to impaired communication with the spinal cord. To compensate for this loss of function, this patient needed to have urine removed every four to six hours by catheterization.

Over eight months Dr. Pohl, the study’s senior author, and colleagues collected 12 urine samples from this patient:

One was collected at a time the patient didn’t show any symptoms of a UTI
Nine were collected when the patient had UTI symptoms, such as bladder spasticity
Two samples were collected when the patient had finished antibiotic treatment for the UTI.

The researchers split each sample in half. One part was put through a standard urinalysis and culture, much like what patients with a suspected UTI would receive at the doctor’s office. The other part was analyzed using a technique that searched for genetic material to identify bacteria that might be present and to estimate their abundance.

The researchers found a variety of different bacteria present in these urine samples. Regardless of the patient’s health status and symptoms, the majority of these bacterial species are known to be pathogenic or potentially pathogenic. By contrast, this patient’s urine microbiome appeared to largely lack bacterial species known to be either neutral or with potentially probiotic properties, such as Lactobacillus.

All of the bacteria that grew in culture also were identified by their genetic material in the samples. However, genetic sequencing also identified a possible novel uropathogenic species called Burkholderia fungorum that didn’t grow in the lab in five of the samples. This bacterium is ubiquitous in the environment and has been identified in soil- and plant-based samples. It also has been discovered in the respiratory secretions of patients with cystic fibrosis, in patients with a heart condition called infectious endocarditis, in the vaginal microbiota of patients with bacterial vaginosis, and in the gut of patients with HIV who have low T-cell counts. Dr. Pohl says it’s unclear whether this species played an infectious role in this patient’s UTI or whether it’s just part of his normal urine flora.

“Consistent with our previous work, this case report demonstrates that rather than healthy urine being sterile, there is a diverse urine bacterial ecosystem during various states of health and disease,” Dr. Pohl says. “Rather than UTIs resulting from the growth or overgrowth of a single organism, it’s more likely that a change in the healthy balance of the urine ecosystem might cause these infections.”

By monitoring the relative abundance of different bacteria types present in the urine of patients with spinal cord injury and combining this information with a patient’s symptoms, Dr. Pohl says doctors may be able to make more accurate UTI diagnoses in this unique population.

In addition to Dr. Pohl, study co-authors include Marcos Pérez-Losada, Ljubica Caldovic, Ph.D., Bruce Sprague and Michael H. Hsieh, M.D., Children’s National; Emma Nally, Suzanne L. Groah and Inger Ljungberg, MedStar National Rehabilitation Hospital; and Neel J. Chandel, Montefiore Medical Center.

Phage therapy draws renewed interest to combat drug-resistant microbes

October 5, 2018

In the face of growing antibiotic resistance and few antibiotics in the development pipeline, phages are drawing renewed research interest as a potential silver bullet.

The married professors were spending their Thanksgiving holiday in Egypt when the husband, Thomas L. Patterson, Ph.D., got very sick very quickly, experiencing fever, nausea and a racing heartbeat. By the time Patterson was accurately diagnosed with a highly multi-drug resistant bacterial infection, he was near death. His wife, Steffanie Strathdee, Ph.D., promised to “leave no stone unturned.’”

What happened next is the ultimate infectious disease feel good story: Strathdee, part of an All-Star team of infectious disease experts and epidemiologists, concocted a cocktail of viruses that killed the superbug and saved Patterson’s life.

“He was going to die,” says Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases at Children’s National Health System. “Because of her epidemiology background – and because she loves him – Patterson became the first patient successfully treated with bacteriophages.”

Dr. DeBiasi explains that all viruses take over cells and use their machinery for their own purposes. In order to escape, viruses blow up the cell. Bacteriophages are viruses that target bacteria, taking over their machinery and ultimately killing the bacterial host.

“Infection is a race between the body’s immune response and the bacteria replicating themselves,” she adds. “Bacteria have to continually replicate. If you knock out 90 percent of them with phage therapy, that gives the immune system a fighting chance to win the race.”

She was so inspired by the team’s ingenuity that DeBiasi, program vice-chair, invited them to recount the story during IDWeek2018, held Oct. 3 to Oct. 7, 2018, in San Francisco. During the closing plenary, Patterson, a professor of psychiatry, and Strathdee, associate dean of Global Health Sciences, will be joined by Robert T. “Chip” Schooley, M.D., (all of University of California, San Diego), to discuss the clinical aspects and efficacy of phage therapy.

About 50 years ago, the U.S. military had investigated leveraging phages but ultimately placed that research portfolio on the back burner. Now, in the face of growing antibiotic resistance and few experimental antibiotics in the development pipeline, phages are drawing renewed research interest as a potential silver bullet.

“The technology has been around for 50 years. We’re going back to old things because we’re so desperate,” Dr. DeBiasi adds.

The tricky thing with phages is that each bacterium needs its own tailored phage therapy.

Children’s National is working with Adaptive Phage Therapeutics, a company based in Gaithersburg, Maryland, that developed the phage used to save Patterson, in order to help build out that library of phages, each ready to be directed to do battle against a specific pathogen.

“We have been consultants to them to think about what would be a good clinical trial, particularly in a pediatric population,” Dr. DeBiasi says.

Children’s National has been collecting and sending isolates from patients with neurogenic bladder who experience urinary tract infections to shore up the phage library in anticipation of a clinical trial. The work builds on Children’s experience as the first center to use phage therapy in a pediatric patient, a 2-year-old who had multidrug-resistant Pseudomonas aeruginosa infection complicated by bacteremia/sepsis.

Understanding antibiotic resistance in patients with cystic fibrosis

September 27, 2018

Patients with cystic fibrosis who carried antibiotic-resistant bacteria, such as Staphylococcus aureus, in their lungs had significantly lower microbial diversity and more aggressive disease, according to a small study published in Heliyon.

A defective gene causes thick, sticky mucus to build up in the lungs of patients with cystic fibrosis (CF). There, it traps bacteria, causing patients to develop frequent lung infections that progressively damage these vital organs and impair patients’ ability to breathe.

Most patients with this progressive genetic disorder die by the fourth decade of life. A key to helping patients live even that long – a vast improvement from an average lifespan of 10 years just decades ago – is judicious use of antibiotics, explains Andrea Hahn, M.D., a pediatric infectious diseases specialist at Children’s National Health System.

But antibiotics are a double-edged sword, Dr. Hahn adds: Although they’re necessary to eradicate lung infections, repeated use of these drugs can lead to antibiotic resistance, making it tougher to treat future infections. Also, antibiotic use can kill the nonpathogenic bacteria living in the lungs as well. That decreases the diversity of the microbial community that resides in the lungs, a factor associated with disease progression. But how antibiotic resistance impacts the relationship between lung bacterial diversity and CF patients’ pulmonary function has been unknown.

Dr. Hahn and colleagues investigated this question in a small study that was published online Sept. 17, 2018, in Heliyon. Their findings suggest that the presence of multidrug resistant bacteria in the airways of patients with CF is associated with decreased microbial diversity and decreased pulmonary function.

In the study, the researchers recruited six patients with CF from Children’s National during well-child visits. During those appointments, the research team collected respiratory secretions from these volunteers. They collected more samples at subsequent visits, including:

When patients were admitted to the hospital for pulmonary exacerbations (periods when infections inflamed their airways, making it difficult to breathe);
Just after intravenous antibiotic courses to treat these infections; and
Thirty days after patients completed antibiotic therapy, when their lungs’ bacterial flora had some time to bounce back.

Over the 18-month study period, these patients made multiple visits for exacerbations and antibiotic treatments, leading to samples from 19 patient encounters overall.

The scientists then analyzed each sample in two different ways. They used some to grow cultures in petri dishes, the classic method that labs use to figure out which bacterial species are present and to determine which antibiotics are effective in tamping them down. They used another part of the sample to run genetic analyses that searched for antibiotic resistance genes. Both methods were necessary to gather a complete inventory of which antibiotic-resistant bacteria were present, Dr. Hahn explains.

“Laboratory cultures are designed to grow certain types of bacteria that we know are problematic, but they don’t show everything,” she says. “By genetically sequencing these samples, we can see everything that’s there.”

Their results revealed a host of bacterial species present in these patients’ airways, including methicillin-resistant Staphylococcus aureus, a notoriously hard-to-treat microbe. Patients who carried this or other antibiotic-resistant bacteria had significantly lower microbial diversity in their samples and more aggressive disease. Their samples also were more likely to contain bacteria of the genus Alcaligenes, whose role in CF is not yet known.

Although heavy antibiotic use probably contributed to both the antibiotic resistance and lowered microbial diversity, Dr. Hahn says, the answer isn’t to reduce use of these drugs: They’re necessary to help patients with CF recover after each bout with pulmonary exacerbations. Rather, she says, using methods beyond a simple lab culture can help doctors target infectious bacteria more selectively, perhaps avoiding collateral damage.

“We can’t stop using antibiotics,” she says, “but we can learn to use them better.”

In addition to Dr. Hahn, Children’s co-authors include Aszia Burrell; Hani Fanous; Hollis Chaney, M.D.; Iman Sami Zakhari, M.D.; Geovanny F. Perez, M.D.; Anastassios C. Koumbourlis, M.D., MPH; and Robert J. Freishtat, M.D., MPH; and Senior Author, Keith A. Crandall, of The George Washington University.

Financial support for the research described in this post was provided by the National Institutes of Health National Center for Advancing Translational Sciences under award number UL1TR000075 and the National Heart, Lung and Blood Institute under award number K12HL119994.

How our bladder’s microbiota affect health

May 30, 2018

The presence of bacteria such as Staphylococcus in the urine is linked to the incidence and severity of urge urinary incontinence as well as treatment success.

About half of the cells in our bodies aren’t really “ours” at all. They’re the microbiota: The vast array of microorganisms that live in our gut, skin, oral cavity and other places. Decades ago, researchers thought that these organisms simply happened to colonize these areas, playing only a tangential role in health, for example, helping to break down food in the intestines or causing cavities. More recent work has revealed the incredibly complex role they play in diseases ranging from diabetes and schizophrenia.

The bladder is no exception. Just a single decade ago, the bladder was thought to be a sterile environment. But that view has shifted radically, with more sensitive cultivation methods and precise 16S rRNA gene-sequencing techniques revealing a significant bladder microbiome that could have an enormous impact on pediatric urologic diseases. These findings have opened brand new fields of research aimed at clarifying the role that the bladder’s microbiome plays in common urological diseases that affect children, according to a review article published online Feb. 22, 2018, by Current Urology Reports.

“There is a growing appreciation for the role of diverse bacteria in contributing to improved health as well as triggering disease processes or exacerbating illness,” says Michael H. Hsieh, M.D., Ph.D., director of the Clinic for Adolescent and Adult Pediatric Onset Urology (CAPITUL) at Children’s National Health System and study senior author. “Already, we know that probiotics and dietary modifications have the potential to play powerful roles in preventing urinary diseases that commonly occur among pediatric patients,” Dr. Hsieh says. This underscores the importance of conducting even more studies to improve our understanding and to identify new therapies for health conditions that resist current treatment options.”

The review conducted by Dr. Hsieh and co-authors highlights the effects of the microbiome on a number of urologic diseases that affect children, including:

Urinary tract infection A number of studies point to the association between decreased microbial diversity and the incidence of what is commonly called urinary tract infection (UTI) or “dysbiosis.” This relationship suggests that using probiotics to replace or supplement antibiotics could favorably alter the urinary microbiome. Future research will focus on the pathophysiological role of the microbiome to determine whether it can be manipulated to prevent or treat UTIs.
Urge urinary incontinence While data vary by study, the presence of bacteria in the urine, especially certain bacterial species – such as Gardnerella, Staphylococcus, Streptococcus, Actinomyces, Aerococcus, Corynebacterium and Oligella – are linked to the incidence and severity of urge urinary incontinence (UUI) as well as treatment success. Most studies find an association between greater genitourinary biodiversity and reduced incidence and lessened severity of UUI as well as improved treatment response. Future research will focus on further clarifying this relationship.
Urolithiasis Calcium oxalate stones, the most common type of kidney stone, have a microbiome that differs from the urinary microbiome leading researchers to question whether the stone’s own bacterial makeup could help to predict recurrence of future kidney stones. What’s more, Oxalobacter formigenes, a gram-negative bacterium, lowers oxalate levels in the blood and are associated with a 70 percent reduction in the risk of kidney stones forming. In an experimental model, fecal transplants with the full microbiome represented had a pronounced and persistent effect on oxalate production. Patients who receive some antibiotics often have reduced rates of formigenes colonization. However, the bacteria are resistant to amoxicillin, augmentin, ceftriaxone and vancomycin, which could point to preferential use of these antibiotics to stave off disease and ward off kidney stone formation.

Additional authors include Daniel Gerber, study lead author, The Georgetown University School of Medicine and Health Sciences; and Catherine Forster, M.D., study co-author, Children’s National.

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