MSGID: 1:317/3 6274a4bb   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   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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