Gut bacteria and urinary infections linked, offering new angles for treatment

By Tarun Sai LomteReviewed by Benedette Cuffari, M.Sc.Apr 30 2024

In a recent study published in the journal eClinicalMedicine, researchers assess the relationship between urinary tract colonization, gut microbiota, and recurrent urinary tract infection (rUTI).

Study: Gut microbiome correlates of recurrent urinary tract infection: a longitudinal, multi-center study. Image Credit: mi_viri / Shutterstock.com

What causes rUTIs?

An estimated 250 million people worldwide are affected by urinary tract infections (UTIs). In the United States, 60% of females and 13.7% of males experience a UTI in their lifetime.

Furthermore, 24% of affected females experience a recurrent episode within six months. UTIs are most commonly caused by uropathogenic Escherichia coli (UPEC).

In healthy people, commensal gut microbiota can provide colonization resistance by modulating host immunity or through competitive exclusion. Repeated exposure to antimicrobials in rUTIs may increase susceptibility to UPEC colonization.

A recent study found depleted gut microbiome richness in females with rUTI; however, the role of UPEC in the microbiome and the factors contributing to recurrence remain unclear.

About the study

The present study examined the relationship between gut microbiota, urinary tract colonization, and rUTIs. Patients with a symptomatic UTI and urine culture positive for Enterobacteriales were included.

Individuals were excluded if they had intra-abdominal devices, more than one organism in urine, recurrent Clostridiodes difficile infection, intestinal mucosal disruption, pregnancy, irritable bowel disease, and kidney stones. Urine cultures with insufficient growth according to clinical standards were also excluded.

Patients were interviewed to collect data on symptoms, treatment, and medical history. Patients provided urine and stool specimens at recruitment, treatment completion, and multiple time points post-treatment. Patients were allowed to continue in the study after their first recurrent episode.

Processed stool samples were streaked onto selective agar specific to the patient’s identified antibiotic-resistant organism. Metagenomic DNA was extracted to prepare sequencing libraries.

Libraries were pooled and sequenced to a depth of five million reads, with the resultant reads trimmed of adapters and depleted of human contamination. Antimicrobial susceptibility testing (AST) was also performed.

The association between resistance and urinary tract colonization was assessed using Firth’s bias-reduced logistic regression. A UTI episode was classified as UPEC-colonized if the same E. coli lineage was recovered from samples or all isolates from the samples belonged to the same lineage. Univariate and multivariate statistical models were used to explore the relationship of uropathogen colonization with rUTI risk.

Study findings

A total of 125 patients were included in the study, 47 of whom had an rUTI within six months. Twelve patients had a second recurrent episode, whereas seven had a third recurrence.

About 93% of the study participants were female, and approximately 93% of UTI episodes were caused by E. coli. The median follow-up time was 155 days. About 5% of patients were hospitalized at enrollment. Cloudy urine and pain/burning during urination were the most common symptoms.

Nitrofurantoin, cephalosporin, and penicillin were most commonly used to treat UTIs. Overall, 644 stool specimens from 106 patients were sequenced, 331 and 313 samples of which were obtained from patients with and without recurrence, respectively.

Enrollment samples were grouped with published rUTI samples from another study as “UTI.” Samples from healthy adults were used for comparison.

UTI samples had lower species richness than healthy samples. Furthermore, the species-level microbiota composition was not significantly different between healthy and UTI samples.

Eleven genus-level intestinal taxa were differentially abundant between healthy and UTI samples, whereas nine were depleted in UTI samples. UTI samples had a significantly higher abundance of antimicrobial resistance genes.

Gut microbiomes from the first UTI episode were compared to explore differences between rUTI and non-rUTI samples. This analysis did not identify any differences in Shannon diversity and richness between these groups.

Furthermore, species richness was lower during treatment but significantly increased between seven and 14 days post-treatment. At this time point, the gut microbiomes of urinary-tract colonized patients were also distinct from those of non-colonized patients.

The gut microbiome did not differ in taxonomic structure at other time points. Paraprevotella xylaniphila and E. coli were the only intestinal taxa significantly enriched in urinary tract-colonized patients.

Gastrointestinal E. coli from urinary tract-colonized lineages exhibited resistance against 11 of 23 tested drugs and had an elevated AST score. AST scores were not elevated for the corresponding urinary isolates from urinary tract-colonizing lineages.

Conclusions

The current study did not identify specific or independent clinical characteristics associated with rUTIs. Although the gut microbiome in UTI patients was distinct from that of healthy individuals, no significant differences in gut microbiome composition were observed between UTI patients with and without a recurrent episode.

Moreover, subjects with urinary tract colonization exhibited a higher abundance of E. coli at post-treatment time points. Urinary tract colonization was also associated with greater resistance among gut isolates but not urinary isolates.

Overall, the study findings suggest that cross-habitation of UPEC could be an essential mechanism for rUTI. Therefore, UPEC populations in the gut and urinary tract should be considered for treatment and when developing novel therapeutics.