Department of Comparative Biosciences chair Chad Vezina works with students in his research lab at the School of Veterinary Medicine.
The number of urinary tract infections (UTIs) diagnosed worldwide each year has exploded in recent decades. In 1990, there were 250 million UTI cases across the world, according to a team of researchers at Shandong University in Jinan, China. By 2019, that figure was more than 400 million — a 60% increase — and researchers believe that estimate is an undercount.
But as more and more people, especially women, grapple with these uncomfortable and sometimes life-altering infections, what if there was a way to encourage the body to naturally fight against UTIs? And what if it was possible to improve how the infections are diagnosed? New research from scientists at the School of Veterinary Medicine (SVM), led by Chad Vezina (Chair, Department of Comparative Biosciences), could hold the answers to both of those questions.
Long considered to be just a passive conduit for urine, the researchers hypothesized that the urethra plays an active role in fighting against UTIs. The urethra contains many of the same cells as the lungs, the intestine and the skin — other organs that interact with the outside world. That got the researchers wondering if certain cells in the urethra would mount a response to potential infections in the same way that they do in other organs, Vezina says.
Vezina and his team tested the theory in mice. They found that bacteria (the most common cause of UTIs) entering the urethra causes certain cells, known as neuroendocrines cells, to release serotonin. That chemical response, in turn, causes the urethra to contract and expel “invading” bacteria.
The discovery leaves Vezina optimistic that there could be ways to bolster the body’s natural response to UTIs. There are existing drugs — many of them antidepressants — that boost the action of serotonin more than naturally would occur.
Those drugs “might be able to help people fight UTIs by boosting the signal” and helping the urethra contract to expel bacteria before it can cause an infection, Vezina says. This presents a potential alternative to combat UTIs at a critical time, given that the bacteria that causes the infections is becoming increasingly resistant to antibiotics.
Vezina’s research, in part, stems from the SVM’s federal designation as a George M. O’Brien center for excellence studying benign urology. The SVM, alongside Columbia and Stanford universities, is a national leader in urological research.
Through a collaboration with Columbia University, the research Vezina’s team conducted was supported by federal funds. But a recent loss of that grant funding leaves additional research the team hoped to conduct about serotonin signals in the urethra with no path forward.
The research could also lead to an improved diagnostic method for patients experiencing UTIs, says Marcela Ambrogi (PhD’20), who worked on the research alongside Vezina.
“A lot of times women go to the doctor and they’re told, ‘No, I’m sorry, but you don’t have a UTI,’” Ambrogi says. “They feel pain, they go to the doctor, and the doctor says there are no signs of bacteria in their urine so they can’t get treated.”
But in many cases, women will return to the doctor several days or weeks later, still experiencing systems, and the bacteria will be detected in urine samples because the infection has progressed, Ambrogi says.
Research done while working toward her PhD showed Ambrogi that mice that were experiencing UTIs had increased serotonin levels in their urine. Accordingly, urine samples from UTI patients could be analyzed for serotonin levels, rather than the presence of bacteria, and allow for treatment to start sooner.
An innovative diagnostic method could also be used to improve animal health, the researchers say.
“We’re looking at whether we can use the breakdown product of serotonin as a signal to identify infections in dogs that come to UW Veterinary Care,” Vezina says, adding that’s especially helpful in the animal health care setting because dogs can’t tell you their symptoms. A more definitive diagnostic method could similarly improve care for pets by reducing the amount of time they endure UTIs before receiving treatment.
By Jack Kelly