Decreased microbiota diversity associated with urinary tract infection in a trial of bacterial interference

Abstract

Background: Patients with long-term indwelling catheters are at high risk of catheter-associated urinary tract infection (CAUTI). We hypothesized that colonizing the bladder with a benign Escherichia coli strain (E. coli HU2117, a derivative of E. coli 83972) would prevent CAUTI in older, catheterized adults.

Materials and methods: Adults with chronic, indwelling urinary catheters received study catheters that had been pre-coated with E. coli HU2117. We monitored the cultivatable organisms in the bladder for 28 days or until loss of E. coli HU2117. Urine from 4 subjects was collected longitudinally for 16S rRNA gene profiling.

Results: Eight of the ten subjects (average age 70.9 years) became colonized with E. coli HU2117, with a mean duration of 57.7 days (median: 28.5, range 0-266). All subjects also remained colonized by uropathogens. Five subjects suffered invasive UTI, 3 febrile UTI and 2 urosepsis/bacteremia, all associated with overgrowth of a urinary pathogen. Colonization with E. coli HU2117 did not impact bacterial bladder diversity, but subjects who developed infections had less diverse bladder microbiota.

Conclusions: Colonization with E. coli HU2117 did not prevent bladder colonization or subsequent invasive disease by uropathogens. Microbial diversity may play a protective role against invasive infection of the catheterized bladder.

Trial registration: ClinicalTrials.gov, NCT00554996 https://ichgcp.net/clinical-trials-registry/NCT00554996.

Keywords: Biodiversity; Microbiome; Microbiota; Probiotics; Urinary tract infection.

Published by Elsevier Ltd.

Figures

Figure 1

Subjects who developed infections had lower microbial diversity. A. Observed OTUs (alpha diversity) in urine samples from subjects that developed an infection compared to samples from subjects who did not develop an infection. B. Observed OTUs in urine samples from subjects colonized and not colonized by E. coli HU2117. C. Shannon Diversity Index of urine samples from subjects that developed infection compared to subjects who did not develop an infection. D. Shannon Diversity Index of samples from subjects colonized and not colonized by E. coli HU2117. P values were obtained using the Mann Whitney test.

Figure 2

Relative abundance of identified genera. A. Identified genera in urine samples from Subject 3, colonized but not infected. B. Identified genera in samples from Subject 9, both colonized and infected. C. Identified genera in samples from Subject 10, neither colonized nor infected. D. Identified genera in samples from Subject 11, not colonized but became infected. Other refers to grouped organisms with species abundance of