Why are some postmenopausal women more prone to recurrent UTIs?

Researchers studying recurrent urinary tract infections in women are tracking the microbiome in bladders in an effort to find an alternative to antibiotics.

Urinary tract infections are among the most common bacterial infections in adults but pose a very significant burden on women – more than 50% suffer a UTI in their lifetimes.

UTIs also disproportionately affect older people, as age is one of the strongest associated risk factors for UTIs.

Now, a new study in postmenopausal women has found that specific bacteria in the bladder may indicate which women are more susceptible to recurrent UTIs, and that estrogen may play a role in reducing that susceptibility.

The study involved 75 postmenopausal women, including those that did not have a history of UTIs, and those who did have recurrent UTIs and were either experiencing one at the time of testing, or were not.

The research team used a whole genome metagenomic sequencing survey to analyse the total DNA of the urogenital microbiome in urine samples from these women.

A history of UTIs had left its mark on the women’s microbiome.

“What we found is that those women who are in between infections — those with a history of recurrent UTIs but currently UTI negative — had a microbiome that was full of microorganisms capable of causing disease of the urinary tract while having fewer good bacteria,” explains first author Dr Michael Neugent, a postdoctoral fellow in De Nisco’s lab.

They also found that there was an association between the use of estrogen hormone therapy and the absence of these “bad” bacterial species and the presence of “good” bacteria such as Lactobacilli.

“We found a very strong association between beneficial bacteria in the bladder and the use of estrogen hormone therapy in postmenopausal women,” says senior author Dr Nicole De Nisco, assistant professor of biological sciences in the School of Natural Sciences and Mathematics at the University of Texas at Dallas (UTD) in the US.

“Estrogen is important not just in regulating reproductive processes, but also in shaping the chemical environment of the entire body. When you lose that hormone, you lose all the benefits that it provides.”

Relying less on antibiotics for treating UTIs

The researchers also found that the microbiomes of women with recurrent UTIs contained more antibiotic resistance genes than those with no history of UTIs. Because antibiotic resistant genes can be spread rapidly from bacteria to bacteria this can result in more difficult to treat infections.

De Nisco says that prescribing antibiotics when they’re not needed, and therefore accelerating antibiotic resistance, will be one of the biggest hurdles to treating UTIs.

“We just can’t throw antibiotics at this problem or else we will never break the cycle of recurrent infections,” De Nisco says.

“We need to start thinking about out-of-the-box therapies that don’t rely so heavily on antibiotics. Rather, we can use things such as estrogen or maybe we give a combined therapy of estrogen and a probiotic.”

These new finding could potentially guide the development of new screening and prevention tools and modulating or restoring the urogenital microbiome could provide an alternative to antibiotics for the treatment of recurrent UTIs.

De Nisco and her team have now begun a five-year longitudinal study to track the microbiomes of postmenopausal women over time.

“This research is meeting a significant unmet need, which is the health of postmenopausal women, who typically have not been a focus of research,” says co-author Dr Kelli Palmer, associate professor of biological sciences at UTD.

“We need more research, novel treatments and generally more public attention on this issue of chronic infections, chronic UTI and older women.”

The research has been published in the journal Cell Reports Medicine.