Recurrent urinary tract infections (rUTI) affect people all around the world and contribute greatly to morbidity, especially for females. In the United States, over one million women seek medical care for rUTIs each year, which are most commonly caused by uropathogenic Escherichia coli (E. coli) and treated with antibiotics. While history of a prior UTI is a significant risk factor, other drivers of rUTI remain unknown. The impact of the microbiome on health and disease is being appreciated in other organ systems. Therefore, this study explored the microbiome connection between the gut and the bladder, or the gut-bladder axis, by characterizing the direct and indirect influences of gut microbiota on the bladder, including the effects of antibiotics to the infection and microbiome.
This longitudinal clinical study was conducted over the course of a year and enrolled women with a history of rUTI (3 or more UTIs in the past 12 months) and women with no history of UTIs for comparison. Blood, urine, and fecal samples were collected from all study participants for analysis. Fecal samples were taken monthly, and additional samples were collected during and post any UTI. Data collected were analyzed with multi-omics techniques to determine diversity of gut microbiota, biomarkers of immune states, and presence of E. coli strains.
The results of the study showed noteworthy differences between women with rUTIs and their healthy counterparts that may inform future treatment options. Women with history of rUTI had less diversity in their gut microbiota and markers of low-level inflammation. Results also showed that women with history of rUTI have different immunological biomarkers compared to women in the healthy cohort, suggesting their immune systems could respond differently to treatment. The transmission of E.coli from gut to bladder was similar in both cohorts, but symptoms only occurred for the women with history of rUTI. However, it was found that the UTI-causing E.coli strains colonized the gut and remained even after antibiotic treatment, potentially explaining reoccurrence of UTIs only in some participants. Furthermore, repeated use of antibiotics may exacerbate gut-bladder imbalance.
The currently used antibiotics and regimens used to treat UTIs and rUTIs may be propagating recurring infections. Antibiotic use reduced gut microbiome diversity and failed to permanently clear uropathogenic E.coli infection, potentially impacting gut-bladder health in women with rUTIs. More specific targeted use of antibiotics, like small molecule therapeutics, may help to improve infections while minimizing disruption to other gut microbiota. Further research is needed to better understand treatment options that also assist in restoring a healthy microbiome.
Reference: Worby CJ, et al. Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women. Nat Microbiol. 2022 May;7(5):630-639. doi: 10.1038/s41564-022-01107-x. Epub 2022 May 2. PMID: 35505248