Antibiotics for UTIs disrupt microbiome, lead to recurrent infections
More than half of women in the United States will experience at least one urinary tract infection (UTI) in their lifetimes, while a quarter will have a recurrent infection. Recurrent urinary tract infections are defined as two or more infections in six months or three or more in a year.
The painful infection is treated by a round of antibiotics. However, a new study has found that women who get recurrent UTIs may be caught in a vicious cycle in which antibiotics required to kill the infection predispose them to develop another.
Cause
A UTI develops when microbes enter the urinary tract and cause infection. Bacteria are the most common cause of UTIs, although fungi rarely can also infect the urinary tract. Most UTIs are caused by Escherichia coli (E. coli) bacteria that live in the bowel and get into the urinary tract.
The research
The year-long study, published in Nature Microbiology, examined 15 women with histories of recurrent UTIs and 16 women without. The participants provided urine and blood samples at the start of the study along with monthly stool samples. The researchers analyzed the bacterial composition in the stool samples, tested the urine for the presence of bacteria, and measured gene expression in blood samples.
Over the course of a year, 24 UTIs occurred, all in participants with histories of repeated UTIs. Once the participants were diagnosed with a UTI, the researchers then took additional urine, blood and stool samples to study.
Findings: Patients with recurrent infections showed decreased diversity of healthy gut microbial species
When the researchers compared who had recurrent UTIs and who did not, it didn’t come down to the kind of E. coli in their intestines or the presence of E. coli in their bladders, but rather the makeup of their gut microbiomes. Patients with recurrent infections showed decreased diversity of healthy gut microbial species, which could provide more opportunities for disease-causing species to thrive and multiply.
It's worth noting that the microbiomes of women with recurrent infections were particularly low 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,” explain Broad Institute scientist Colin Worby, PhD, a computational biologist and the paper’s lead author.
Worby added that the 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.
Alternatives needed
The results underscore the importance of finding alternatives to antibiotics for treating UTIs. The authors floated strategies that would rebalance the microbiome such as fecal transplants, or probiotics.
“This is one of the most common infections in the United States, if not the world,” said co-senior author Scott J. Hultgren, PhD, the Helen L. Stoever Professor of Molecular Microbiology at Washington University. “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.”
Source: Nature Microbiology
02 May 202210.1038/s41564-022-01107-x
“Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women”
Authors: C. Worby, et al.
