The Presumed Link Between the Gut Microbiota and Urinary Tract Infections

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Urinary tract infections (UTIs) are a common medical problem and affect millions of people around the world [1]. A main source for UTI is presumed to be the gut. Gut bacteria is thought to contaminate the urethral opening and eventually propagate itself in the bladder and cause symptoms of a UTI [2]. Although this gut microbiota-UTI axis has been theorized, there is little evidence to support a direct link.

Our laboratory sought out to investigate this first step, the role of the gut microbiota in the development of UTIs. We had the unique opportunity to study kidney transplant recipients at New York Presbyterian Hospital – Weill Cornell Medical Center. We collected serial fecal and urine specimens in the first 3 months after transplantation from 168 kidney transplant recipients. Importantly, kidney transplant recipients have a very high rate of UTI early after kidney transplantation, which allowed us to study fecal specimens prior to the development of UTI. Kidney transplant recipients at our center also have routine conventional urine cultures performed at every clinical visit, allowing us to evaluate bacteriuria (the presence of bacteria in the urine without clinical symptoms) as well as UTI. In this paper, we report that the gut abundance of E. coli was associated with future development of E. coli bacteriuria and E. coli UTI in a multivariable model controlling for important factors such as gender. One question that we also wanted to address was that if there is a link between E. coli in the gut and E. coli in the urine, what would the E. coli look like at the strain level? Would the E. coli strains in the urine group separately from the E. coli strains in the gut or would the E. coli strain in the urine more closely resemble the E. coli strain in the gut from the same subject? We performed strain analysis using StrainPhlAn [3] and found that most E. coli strains in the gut are phylogenetically closer to the E. coli strain in the urine from the same subject, thus supporting the concept that a source of UTI is the gut reservoir.

Our data raises the possibility of manipulation of the gut microbiota, via probiotics or fecal microbial transplantation, for preventing UTIs. While a simple UTI can be treated successfully with antibiotics, many patients have UTI recurrence, which can lead to antibiotic resistance as well as other opportunistic infections like Clostridiodes difficile diarrhea. Indeed, a study by Tariq et al. reported a decrease in UTI recurrence after fecal microbial transplantation for patients with recurrent C. difficile infections who also had recurrent UTIs [4]. We hope that our data provides the impetus for future studies involving modulation of the gut microbiota to prevent and/or treat UTI, which is one of the common medical problems around the world.

Read the full paper here: https://www.nature.com/articles/s41467-019-13467-w

References:

1.    Stamm WE, Norrby SR. Urinary tract infections: disease panorama and challenges. J Infect Dis, 183 Suppl 1, S1-4 (2001).
2.    Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol, 13(5), 269-284 (2015).
3.    Truong DT, Tett A, Pasolli E, Huttenhower C, Segata N. Microbial strain-level population structure and genetic diversity from metagenomes. Genome Res, 27(4), 626-638 (2017).
4.    Tariq R, Pardi DS, Tosh PK, Walker RC, Razonable RR, Khanna S. Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection Reduces Recurrent Urinary Tract Infection Frequency. Clin Infect Dis, 65(10), 1745-1747 (2017).

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John Lee

Assistant Professor, Weill Cornell Medicine

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