Recurrent infections and estrogen can shape the urogenital microbiota

New research indicates that recurrent urinary tract infections and estrogen can shape the urogenital microbiota in ways that may protect against recurrent infections.
Table of Contents

What is already known
More than half of women suffer a urinary tract infection (UTI) in their lifetimes, and about half of those who have gone through menopause and who contract a UTI will have a recurrent infection. Several studies have shown that the urogenital microbiota may play a role in recurrent UTIs, but how changes in the microbiota influence susceptibility to recurrent infections is unknown.

What this research adds
By analyzing urine samples from 75 postmenopausal women, researchers found that those with a history of recurrent UTIs had in their urogenital microbiotas high levels of bacteria that are typically found during an active infection. Women who didn’t suffer from recurrent UTIs had high levels of the hormone estrogen, and their urogenital microbiotas were enriched in Bifidobacterium and Lactobacillus bacteria. The researchers also identified antimicrobial resistance genes that were frequently found in the urogenital microbiotas of women with recurrent UTIs.

Conclusions
The findings suggest that recurrent UTIs and estrogen can shape the urogenital microbiota in ways that may protect against recurrent infections. The results may also help inform better treatments for recurrent UTIs.

More than half of women suffer a urinary tract infection (UTI) in their lifetimes, and about half of those who have gone through menopause and who contract a UTI will have a recurrent infection. New research indicates that recurrent UTIs and estrogen can shape the urogenital microbiota in ways that may protect against recurrent infections.

The findings, published in Cell Reports Medicine, may also help inform better treatments for recurrent UTIs.

Recurrent UTIs are often treated with antibiotics, but the number of UTIs caused by bacteria resistant to most first-line antibiotics is increasing. Alternative therapeutic approaches are needed to improve the clinical outcome and the quality of life of women with recurrent UTIs, the researchers say.

In the past decade, several studies have shown that the urogenital microbiota may play a role in recurrent UTIs, which are defined as more than two UTIs in a six-month period. However, how changes in the microbiota influence susceptibility to recurrent infections is unknown.

To identify such changes, Nicole De Nisco at the University of Texas at Dallas and her colleagues set out to analyze urine samples from 75 postmenopausal women.

Microbial differences

To validate the presence of living microbes within the urogenital microbiotas of participants, the researchers combined urine culture with DNA sequencing. They detected a total of 276 bacterial, archaeal and fungal species across 106 genera. Bacteria represented more than 99% of the urogenital microbiota, with Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes dominating the community.

Women with a history of recurrent UTIs had in their urogenital microbiotas high levels of bacteria that are typically found during an active infection, including uropathogenic Escherichia coli, the major pathogen in most types of UTIs, as well as Klebsiella pneumoniae, Enterococcus faecalis and Streptococcus agalactiae. Instead, in the urogenital microbiotas of women without active UTI, the researchers found mostly Lactobacillus, Bifidobacterium, Gardnerella, Streptococcus, Staphylococcus and Actinobaculum

The team observed that about one in four women without active UTIs had high abundances of Bifidobacterium and Lactobacillus in their urogenital microbiotas. Lactobacillus are probiotic bacteria that may protect against infection.

Estrogen effect

The researchers found that the hormone estrogen was associated with the presence of Lactobacillus bacteria in the urogenital microbiota. Estrogen is thought to promote Lactobacillus colonization of the vaginal and urinary tract.

On the other hand, in the urogenital microbiotas of women with recurrent UTIs, the researchers identified genes that confer resistance to front-line antibiotics, such as trimethoprim-sulfamethoxazole, fluoroquinolones and nitrofurantoin. 

The study, the researchers say, “provides a robust foundation for further mechanistic studies of the role of the urogenital microbiome in [recurrent] UTI susceptibility and disease progression that are necessary for the development of urogenital microbiome-aware alternative therapies for a [recurrent] UTI.”