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Host Genetic, Environmental Factors Influence Composition of Urinary Tract Microbiome

NEW YORK – Both genetic and environmental factors influence the makeup of the urinary tract microbiome of older women, a new analysis has found. 

Urine was previously thought to be sterile in healthy people, but recent studies have found it has a microbiome all its own. To characterize the normal urinary tract microbiome, researchers led by King's College London's Claire Steves analyzed samples from 1,600 healthy women from the TwinsUK cohort. 

As they reported in Cell Host & Microbe on Tuesday, the researchers identified 61 common core urinary tract microbes and noted the urinary tract microbiome was distinct from the stool or vaginal microbiomes. They further found that host genetics influence about a third of the makeup of the urinary tract microbiome, though environmental factors such as age and prior urinary tract infection also influence its composition.

"These findings highlight the distinct composition of the urinary microbiome and significant contributions of host genetics," Steves and her colleagues wrote in their paper.

The researchers performed 16S rRNA sequencing of midstream urine samples from 1,600 mostly post-menopausal women from the TwinsUK cohort. When they compared the composition of these samples to the previously published microbiomes of other body sites, the researchers found the diversity of the urine dataset to be similar to that of the vaginal dataset, but that it was not as diverse as the stool dataset.

As compared to the gut microbiome dataset, the urinary tract microbiome included more Actinobacteria, Fusobacteria, and Proteobacteria, but fewer Bacteroidetes, Firmicutes, and Verrumicrobia.

Within the urinary tract microbiome, the researchers identified a set of 61 core microbial taxa.

Using three different measurements — heritability, family segregation, and ancestry-based analyses — they found a significant effect of host genetics on the composition of the urine microbiome. In particular, for the core microbiome, they found that nearly a quarter of those variants that were found in at least 5 percent of participants had heritability estimates larger than 10 percent. One of these, Escherichia_Shigella, has been implicated in urinary tract infections and suggests host genetics may contribute to such infections.

In all, they estimated that about a third of the variation in the urinary tract microbiome is influenced by genetics.

Other host factors also influenced its composition. Increasing age, the researchers noted, was associated with an overall increase in alpha diversity, and there was also a link between age and beta diversity. The core taxa also differed with age.

While age was the top host-related or environmental factor, other factors such as parity, history of urinary tract infections, and menopause status also affected the urinary tract microbiome.

For a subset of participants, the researchers also generated shotgun metagenomic data in addition to the 16S data. The core microbiome they identified through the 16S data was largely recapitulated in the metagenomic dataset, they reported.

"The urinary microbiome was distinct and apparently unrelated to stool microbiome. It shows a significant contribution of host genetics," the researchers wrote. "Key species known to be clinically relevant were among the most heritable microbes."

The researchers noted, however, that their study was limited by the use of questionnaires to gather data on UTI occurrence and other host factors, and by its reliance on a single urine sample from participants.