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MONDAY, May 9, 2022
Urinary tract infections (UTIs) are common and often easily managed, yet some women are plagued by one infection after another. Now, a new study hints at a culprit: the antibiotics used to treat them.
Exactly why those women suffer repeat bouts has been unclear.
The new study, published May 2 in the journal Nature Microbiology, offers early evidence of a potential reason: The antibiotics used to treat UTIs might set the stage for repeat infections by depleting the gut microbiome of beneficial bacteria.
The makeup of those bacteria is always in flux, being influenced by various factors, from diet to antibiotic use. Anyone who has ever had digestive issues after a course of antibiotics has felt those effects.
The gut is also known to be a "reservoir" for certain bacteria that cause most UTIs -- so-called uropathogenic E. coli. In fact, UTIs often arise from the "ascension" of those bacteria from the gut to the urinary tract, explained Scott Hultgren, one of the senior researchers on the new study.
In theory, throwing off the delicate balance between "good" and "bad" gut bacteria could predispose some women to recurrent UTIs.
But until now, studies have not delved into the question, said Hultgren, a professor of molecular microbiology at Washington University School of Medicine in St. Louis.
So he and his colleagues recruited 31 women ages 18 to 45. Fifteen of them had recurrent UTIs -- three or more in the past year. Over the next year, the researchers collected blood and urine samples, plus monthly stool samples, from the women. During that time, there were 24 more UTIs in the study group, all among women who'd been suffering recurrent bouts, and they were usually treated with antibiotics.
Overall, the researchers found, women with recurrent UTIs had a gut microbiome that looked different from other women's. They had much less diversity in their good bacteria, and fewer microbes that produce butyrate -- a fatty acid that helps control inflammation.
Meanwhile, women in the comparison group were just as likely to show UTI-causing E. coli in their guts, and those bugs sometimes traveled to their bladders. The difference was, those women did not develop UTIs.
According to the researchers, it all suggests that those UTI-free women were able to control the bad bugs, while women with recurrent UTIs were not -- possibly due to the disturbances in their gut bacteria.
One big unknown is how everything is thrown off in the first place, said Ashlee Earl, co-senior researcher on the study. Was it the antibiotic treatment for the first UTI? Or was there a gut microbiome disturbance, for whatever reason, which set women up for the first UTI and the antibiotic worsened the situation?
"To be determined," said Earl, of the Broad Institute of MIT and Harvard in Cambridge, Mass.
A bigger point, she noted, is that this study throws cold water on the traditional notion that recurrent UTIs are a matter of "hygiene."
"There can be a stigma around recurrent UTIs," Earl said. "But this doesn't have to do with hygiene. There is something else going on inside the body."
Dr. Karyn Eilber, a urologist who was not involved in the study, said the findings make sense, and fit with the longstanding concern that antibiotics are probably overused for UTIs.
"But if your doctor recommends an antibiotic," she said, "you can feel free to ask whether it's necessary."
Sometimes it's possible to simply treat symptoms, like using common painkillers to manage abdominal discomfort. Another alternative for recurrent UTIs, Eilber said, is a medication called methenamine. It works by making the urine more acidic and stopping bacterial growth, and studies have shown that it can prevent recurrent UTIs.
Yet another option for some women, Eilber said, is vaginal estrogen: After menopause, the vaginal lining thins, which can foster the growth of bad bacteria there, and sometimes lead to UTIs. Vaginal estrogen counters that, and may prevent recurrent UTIs in some women.
The hope is that additional treatment options will be available in the near future.
"We're trying to develop new compounds to selectively deplete uropathogenic E. coli, while keeping the gut microbiome intact," Hultgren said.
One such compound, based on the sugar mannoside, is currently being tested in a clinical trial.
SOURCES: Ashlee Earl, PhD, senior group leader, Bacterial Genomics Group, Broad Institute of MIT and Harvard, Cambridge, Mass.; Scott Hultgren, PhD, Helen L. Stoever professor, molecular microbiology, Washington University School of Medicine, St. Louis; Karyn Eilber, MD, urologist, Female Pelvic Medicine and Reconstructive Surgery, Cedars-Sinai Medical Center, Los Angeles; Nature Microbiology, May 2, 2022, online
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