A urinary tract infection (UTI) can be maddening. It hurts to urinate; it hurts to not urinate. You don’t dare to stray far from a bathroom. You feel like you’re sloshing in fruit juice and water, trying to flush it out of your body. You need relief. Even more maddening – it keeps recurring, lessening quality of life. A new study may explain the vicious cycle of recurrent infections: an antibiotic used to treat a UTI predisposes the body to another infection thanks to gut bacteria.
UTIs are caused by bacteria in the urinary tract, usually Escherichia coli (E. coli) from the GI tract that contaminate the urinary tract. They generally resolve quickly with antibiotic treatment, but for many patients the relief is temporary. One in four women will develop another UTI within six months. Some patients get UTIs over and over, need an antibiotic over and over, and fear that there is no permanent solution.
Researchers at Washington University School of Medicine in St. Louis, the Massachusetts Institute of Technology, and Harvard collaborated to find causes and solutions for recurrent UTIs. They showed that antibiotics eliminate noxious bacteria from the bladder, but not from the intestines. The gut bacteria can multiply, spread to the bladder, and reseed another UTI.
It is also known that antibiotics alter an individual’s gut microbiome. Like other disorders which link gut microbes with the immune system, the microbiomes of women with recurrent UTIs lack the diversity of the microbiomes in women without recurrent UTIs. That lack includes deficiency in bacteria that help regulate inflammation.
To determine why some women get recurrent infections and others don’t, the researchers studied 15 women with histories of recurrent UTIs and 16 women with no history of UTIs. All participants provided urine and blood samples at the start of the study and monthly stool samples. The team analyzed the bacterial composition in the stool samples and tested the urine for the presence of bacteria.
There were 24 UTIs diagnosed during the year-long study, all in participants with histories of recurrent UTIs. Participants who were diagnosed with a UTI provided additional urine, blood, and stool samples.
The team conjectured that the difference between the women who got repeated UTIs and those who didn’t would be attributable to differing strains of E. coli in their GI tracts, or the presence of E. coli in their bladders. They were wrong. Both groups carried E. coli strains which could cause UTIs. These strains occasionally spread to their bladders.
The difference, however, was in the composition of their gut microbiomes. Patients with repeat infections showed less diversity of beneficial gut microbial species. The lack of diversity allowed more disease-causing species of bacteria to inhabit and multiply in the bladder. The microbiomes of women with recurrent UTIs were particularly deficient in bacteria that produce butyrate, a short-chain fatty acid with anti-inflammatory effects.
“We think that women in the control group were able to clear the bacteria from their bladders before they caused disease, and women with recurrent UTI were not, because of a distinct immune response to bacterial invasion of the bladder potentially mediated by the gut microbiome,” says Colin Worby, PhD, a computational biologist at Wash U, in a statement.
The findings support the importance of finding alternatives to antibiotics for treating UTIs. “Our study clearly demonstrates that antibiotics do not prevent future infections or clear UTI-causing strains from the gut, and they may even make recurrence more likely by keeping the microbiome in a disrupted state,” Worby said.
Scott J. Hultgren, PhD, a professor of molecular microbiology at Washington University, has devoted much of his work to finding innovative therapies which eliminate disease-causing strains of E. coli but spare the rest of the gut microbiome. His research has generated an experimental drug and an investigational vaccine. Both are now in clinical trials.
“This is one of the most common infections in the United States, if not the world,” Hultgren said. “A good percentage of these UTI patients go on to get these chronic recurrences, and it results in decreased quality of life. There is a real need to develop better therapeutics that break this vicious cycle.”
The study is published in the journal Nature Microbiology.