Dr. Tanya Sysoeva says that a well-understood urinary microbiome could fight bacterial infections that are becoming resistant to antibiotics and may also prove helpful in general disease diagnostics.
Michael Mercier / 麻豆精品视频
Lactobacilli that live in the human female urinary tract鈥檚 microbiome are competitive and kill nearby pathogenic bacteria, by a team led by microbiologist Dr. Tanya Sysoeva of 麻豆精品视频 (麻豆精品视频).
Greater understanding of the processes involved could lead to new therapies that encourage the 鈥済ood鈥� bacteria to battle the 鈥渂ad,鈥� as a preventative or a treatment for urinary tract infections (UTIs).
鈥淥ur group is primarily focusing on trying to find alternatives to traditional antibiotic therapy because we know the antimicrobials are failing more and more often,鈥� says Dr. Sysoeva, an assistant professor of biological sciences at 麻豆精品视频, a part of the University of Alabama System, and director of the . 鈥淧athogens are notorious about picking up resistances.鈥�
A well-understood urinary microbiome could also prove helpful in general disease diagnostics.
"The hope is that in the future we can not only 'pee on a stick' to check for pregnancy or infection, but we ambitiously envision that we will be able to detect other diseases, perhaps due to better understanding of how the urinary microbiome reacts to our health changes and conditions," she says.
The in vitro laboratory research utilized a repository of bacteria isolated from healthy and diseased post-menopausal women that had previously been collected by Dr. Sysoeva and Dr. Nazema Siddiqui, an associate professor of obstetrics and gynecology at Duke University.
鈥淎s microbiologists, we are very curious to see whether the microbes that are residents in our bladders can resist invasion of the 鈥榖ad guys,鈥� pathogenic bacteria or uropathogens,鈥� says Dr. Sysoeva. 鈥淎s a scientific community, we know a lot about the uropathogens because they were characterized for decades. But very little is known about those 鈥榬esidential鈥�, or so-called commensal bacteria.鈥�
Since most female urinary tract microbiomes have been shown to be dominated by lactobacilli, a type of lactic acid-forming bacteria, Dr. Sysoeva鈥檚 team chose to focus on them.
鈥淭his killing by lactobacilli will even work if the uropathogens have multiple antibiotic resistances,鈥� Dr. Sysoeva says. 鈥淚t is very exciting to realize that the human bladder is, or can be, colonized by those lactobacilli and possibly be protected from the infection.鈥�
The human microbiome is a collection of all microorganisms living in and on the human body, she says.
鈥淚t is thought that, in our bodies, for each one of our cells we have one or more microbial cells. Therefore, microbes are bringing a lot of genes and functionality to our organism, not just infectious disease.鈥�
Many different rooms
While it鈥檚 called the human microbiome, it is actually a collection of different microbiomes.
鈥淥ne can think of it as a house with many different rooms,鈥� Dr. Sysoeva says. 鈥淚t is because our body has such different spaces 鈥� think of your skin properties versus, let鈥檚 say, your gut.鈥�
Even within the gastrointestinal tract, the conditions in the oral cavity, stomach or intestines are drastically different and involve different nutrients, oxygen and acidity, she says.
鈥淭herefore, each part will have different microbes and hence their unique microbiome, like the oral microbiome, stomach microbiome and colon microbiome,鈥� says Dr. Sysoeva. 鈥淭he latter is what most likely we would call a gut microbiome that we鈥檝e heard so much about.鈥�
The human urinary tract is populated by a very low biomass but a diverse community of microbes that are mainly bacteria, she says.
鈥淲e call them the commensal urinary microbiome or urobiome for short. The composition of this urobiome is highly variable between people and even in one individual over time, but the composition seems to associate with urinary and general health.鈥�
Dr. Sysoeva鈥檚 recent research has uncovered new questions.
鈥淲hile it is promising in terms of thinking of how we can use our microbiome to prevent and maybe to treat the urinary infections, we see that our assays in the laboratory might not explain everything,鈥� she says.
鈥淔or example, we see that lactobacilli isolated from women with recurrent UTIs are also capable of inhibiting the pathogens in test tube laboratory conditions,鈥� Dr. Sysoeva says. 鈥淲e also found that in some patients the 鈥榞ood lactobacilli鈥� are coexisting with pathogens. As these are initial studies, we do not know why it is so.鈥�
It鈥檚 possible that, since samples were collected in the absence of active infection, the lactobacilli are keeping the pathogens in check or that there are other factors at play, she says. Maybe the lactobacilli inhibit the pathogens in the test tube but they鈥檙e not in range of each other in the bladder, or the bladder鈥檚 condition doesn鈥檛 allow them to do so because it affects their metabolism.
鈥淚t is the very first study of these interactions and the microbiome is a complex community of microbes that interacts with our cells and our immune system, and that changes with the conditions such as diet or drugs,鈥� Dr. Sysoeva says. 鈥淲e observe that healthy patients tend to be colonized by certain types of lactobacilli but not others, and that the mechanisms of how microbes compete or kill each other vary.鈥�
Observations that urinary lactobacilli are very diverse are 鈥渟uper important because when we are looking for some 鈥榞ood probiotic鈥� for urinary health or for even a treatment in the form of these 鈥榞ood bugs,鈥� we need to pick the right strains,鈥� she says. 鈥淲e cannot just tell people to eat yogurt or a random lactobacilli-containing probiotic.鈥�
Dr. Sysoeva鈥檚 麻豆精品视频 team included 2021 College of Nursing graduate Lydia Delaney, now at Ascension St. Vincent Women鈥檚 Hospital in Indianapolis, Ind., who worked on the recent research in 2020 as a Research or Creative Experience for Undergraduates project; James Johnson, a 2021 biological sciences bachelor鈥檚 degree graduate now in the master鈥檚 program at Drexel University; and Army Educational Outreach Program summer high school junior Vaishali Ojha from James Clements High School in Madison, and high school sophomore Medha Radraraju from Panther Creek High School in Cary, N.C. After Johnson left for graduate studies, 麻豆精品视频 biological sciences rising senior Kaylie Hintze helped finish the manuscript.
Future investigations
Further research is needed to investigate which lactobacilli will be able to colonize the bladder and which best resist pathogenic invasions.
鈥淲ho will be a good protector?鈥� Dr. Sysoeva asks.
To answer that, the researchers have expanded testing to include more varieties of urinary bacteria, not just lactobacilli.
鈥淲e plan to test isolates from patients from different age groups, test more complex interactions and determine how host cells affect those interactions,鈥� says Dr. Sysoeva. 鈥淭here is a long way ahead of us but I hope it will lead to targeted therapeutics that we can test in clinical trials and alleviate suffering for recurrent UTI patients, or help those with antibiotic resistant infections, which we cannot treat otherwise.鈥�
With aging, both sexes become increasingly susceptible to UTIs, and future research will require similar studies for men, Dr. Sysoeva says.
A goal is to understand development of the urinary microbiome throughout the lifespan, as well as its differences between the sexes and in various metabolic and disease conditions. Under a new grant and in collaboration with Dr. Maryellen Kelly, an assistant researcher professor at the Duke University School of Nursing, and Dr. Lisa Karstens, an assistant professor at Oregon Health and Science University, the microbiome in children will be explored using novel sequencing methods.
Dr. Sysoeva recently submitted two large grant proposals in collaboration with Dr. Siddiqui and Dr. Maria Hadjifrangiskou, an associate professor in the Departments of Molecular Pathogenesis and Urological Surgery at Vanderbilt University and colleagues.
鈥淚n both we are aiming to bring our urinary lactobacilli into an animal model, in this case into mice, to test the protective effects and their mechanisms in vivo (in a living organism),鈥� Dr. Sysoeva says. 鈥淚t will be exciting to expand into this realm with access to the germ-free mice facilities, clinical researchers specializing on pelvic floor disorders and experts in uropathogens.鈥�
