Saturday, December 10, 2022

Recurrent UTI, chronic inflammation associated with gut microbiome: Antibiotics may increase risk of further UTIs by disrupting microbiome

One of the biggest frustrations with regards to urinary tract infections (UTIs) is that they often recur. UTIs are caused by bacteria in the urinary tract and cause frequent and painful urination. A round of antibiotics usually clears up symptoms, but relief is often temporary: A quarter of women develop a second UTI within six months. A few unfortunate individuals have recurrent UTIs, and need antibiotics every few months.

A new study suggests that women who have recurrent UTIs may be caught in a vicious cycle in which antibiotics given to clear one infection lead them to develop another. The study, conducted by researchers at Washington University School of Medicine in St. Louis and the Broad Institute of MIT and Harvard, showed that a single round of antibiotics eliminate disease-causing bacteria from the bladder, but not from the intestines. Bacteria that survive 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, were deficient in an important group of bacteria that help control inflammation, and had a higher concentration in their blood. There was a sign of distinct immunological signature. inflammation.

The study is published on 2 May Nature Microbiology.

“It’s frustrating for women who are coming to the doctor after recurrence after recurrence, and doctors, who are usually men, give them advice about hygiene,” said co-senior author Scott J. Hultgren, PhD, Helen L. Stover Professor of Molecular Microbiology at the University of Washington. “It’s not necessarily what the problem is. It’s not necessarily the poor hygiene that’s causing it. The problem lies in the disease itself, the relationship between the gut and the bladder, and the level of inflammation. Basically, physicians don’t know.” That’s what to do with recurrent UTIs. They only have antibiotics, so they throw more antibiotics at the problem, which probably makes things worse.”

What are the causes of most UTIs? Escherichia coli ,e coli) bacteria from the intestines that enter the urinary tract. To understand why some women get the infection post-infection and others get one or none, Holtgren asked Broad Institute scientists Ashley Earl, PhD, senior group leader in the Bacterial Genomics Group at Broad and co-author of the paper. -Senior writer and collaborated with Colin Varby. , PhD, a computational biologist and lead author of the paper.

Researchers studied 15 women with a history of recurrent UTIs and 16 women without. All participants provided urine and blood samples and monthly stool samples at the start of the study. The team analyzed the composition of bacteria in stool samples, tested urine for the presence of bacteria, and measured gene expression in blood samples.

Over the course of one year, 24 UTIs occurred, in all participants with a history of recurrent UTIs. When the participants were diagnosed with a UTI, the team took additional urine, blood and stool samples.

The difference between women who had recurrent UTIs and those who did not, was not surprisingly narrow. e coli in their intestines or even in the presence of e coli in their bladder. both groups took e coli The strains in their intestine are capable of causing UTIs, and such strains sometimes spread to their bladders.

The real difference was in the makeup of their gut microbiome. Patients with repeated infections showed a reduction in the diversity of healthy gut microbial species, which may provide more opportunities for disease-causing species to gain a foothold and multiply. Notably, the microbiomes of women with recurrent UTIs were particularly rare 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 bacteria from their bladders before they caused disease, and women with recurrent UTIs were not, because of a different immune response to bacterial invasion of the bladder, potentially by the gut microbiome. There is a mediator,” said Vorby.

The findings highlight the importance of finding alternatives to antibiotics to treat UTIs.

“Our study clearly demonstrates that antibiotics do not prevent future infections or clear UTI-causing strains from the gut, and they may make recurrences more likely by keeping the microbiome in a disrupted state,” said Verby. said

Hultgren has long worked on finding innovative treatments to eradicate disease-causing strains e coli from the body while sparing the rest of the bacterial community. Their research forms the basis of an experimental drug and an investigational vaccine based on the Chinese mannoside, which are being tested in people. Another strategy would be to rebalance the microbiome through fecal transplant, probiotic foods or other means.

“This is one of the most common infections in the United States, if not the world,” Holtgren said. “A good percentage of these UTI patients go on to get these chronic recurrences, and this results in decreased quality of life. There is a real need to develop better therapeutics that break this vicious cycle.”


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