Recurrent UTIs linked to gut microbiome, chronic inflammation
Antibiotics may increase risk of further UTIs by disrupting microbiome


Date:
May 5, 2022
Source:
Washington University School of Medicine
Summary:
A study suggests that women who get recurrent urinary tract
infections (UTIs) may be caught in a vicious cycle in which
antibiotics given to eradicate one infection predispose them to
develop another.



FULL STORY ==========================================================================
One of the greatest frustrations regarding urinary tract infections
(UTIs) is that they so often recur. UTIs are caused by bacteria in the
urinary tract and characterized by frequent and painful urination. A
round of antibiotics usually clears up the symptoms, but the relief
is often temporary: A quarter of women go on to develop a second UTI
within six months. Some unfortunate individuals get UTIs over and over,
and require antibiotics every few months.


==========================================================================
A new study suggests that women who get recurrent UTIs may be caught in
a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. The study, by researchers at
Washington University School of Medicine in St. Louis and the Broad
Institute of MIT and Harvard, showed that a round of antibiotics
eliminates disease-causing bacteria from the bladder but not from the intestines. Surviving bacteria in the gut can multiply and spread to
the bladder again, causing another UTI.

At the same time, repeated cycles of antibiotics wreak havoc on the
community of helpful bacteria that normally live in the intestines, the so-called gut microbiome. Similar to other disorders in which gut microbes
and the immune system are linked, women with recurrent UTIs in the study
had less diverse microbiomes that were deficient in an important group of bacteria that helps regulate inflammation, and a distinct immunological signature in their blood indicative of inflammation.

The study is published May 2 in Nature Microbiology.

"It's frustrating for women who are coming in to the doctor with
recurrence after recurrence after recurrence, and the doctor, who's
typically male, gives them advice about hygiene," said co-senior author
Scott J. Hultgren, PhD, the Helen L. Stoever Professor of Molecular Microbiology at Washington University.

"That's not necessarily what the problem is. It's not necessarily poor
hygiene that's causing this. The problem lies in the disease itself,
in this connection between the gut and the bladder and levels of
inflammation. Basically, physicians don't know what to do with recurrent
UTI. All they have is antibiotics, so they throw more antibiotics at
the problem, which probably just makes things worse." Most UTIs are
caused by Escherichia coli (E. coli) bacteria from the intestines that
get into the urinary tract. To understand why some women get infection
after infection and others get one or none, Hultgren teamed up with Broad Institute scientists Ashlee Earl, PhD, the senior group leader for the Bacterial Genomics Group at Broad and the paper's co-senior author, and
Colin Worby, PhD, a computational biologist and the paper's lead author.



==========================================================================
The researchers studied 15 women with histories of recurrent UTIs and
16 women without. 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, 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. When participants were diagnosed with a UTI,
the team took additional urine, blood and stool samples.

The difference between the women who got repeated UTIs and those who
didn't, surprisingly, didn't come down to the kind of E. coli in their intestines or even the presence of E. coli in their bladders. Both
groups carried E. coli strains in their guts capable of causing UTIs,
and such strains occasionally spread to their bladders.

The real difference was in the makeup of their gut microbiomes. Patients
with repeat infections showed decreased diversity of healthy gut microbial species, which could provide more opportunities for disease-causing
species to gain a foothold and multiply. Notably, the microbiomes of
women with recurrent UTIs were particularly scarce 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," Worby said.

The findings highlight 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 Hultgren has long worked on finding innovative
therapies to eradicate disease- causing strains of E. coli from the body
while sparing the rest of the bacterial community. His research forms
the basis of an experimental drug based on the sugar mannosideand an investigational vaccine, both of which are being tested in people. Another strategy would be to rebalance the microbiome through fecal transplants, probiotic foods or other means.

"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."

========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Tamara
Bhandari. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Colin J. Worby, Henry L. Schreiber, Timothy J. Straub, Lucas
R. van Dijk,
Ryan A. Bronson, Benjamin S. Olson, Jerome S. Pinkner, Chloe L. P.

Obernuefemann, Vanessa L. Mun~oz, Alexandra E. Paharik, Philippe N.

Azimzadeh, Bruce J. Walker, Christopher A. Desjardins, Wen-Chi
Chou, Karla Bergeron, Sine'ad B. Chapman, Aleksandra Klim, Abigail
L. Manson, Thomas J. Hannan, Thomas M. Hooton, Andrew L. Kau,
H. Henry Lai, Karen W.

Dodson, Scott J. Hultgren, Ashlee M. Earl. Longitudinal multi-omics
analyses link gut microbiome dysbiosis with recurrent urinary tract
infections in women. Nature Microbiology, 2022; 7 (5): 630 DOI:
10.1038/ s41564-022-01107-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/05/220505180921.htm

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