The incidence of urinary stone disease (USD) and other chronic inflammatory diseases, including obesity and cardiovascular disease, has increased over the last several decades. Researchers suspect that dysbiosis—a microbial imbalance caused, in part, by diet and antibiotics—may be a factor. Research recently published in Scientific Reports validates the claim that antibiotics influence a long-term shift in the microbiome that may increase risk for USD. It also establishes the urinary tract microbiome, and not the gut microbiome, as a pathogenic target for USD.
Understanding the urinary tract microbiome
While previous studies have investigated the gut microbiome’s role in USD pathology, little focus has been given to the role of the urinary tract microbiome. “This is the first metagenomics study, to our knowledge, to actually compare the urinary tract microbiome between healthy populations and USD patients,” says Aaron Miller, PhD, Project Scientist, Lerner Research Institute and Glickman Urologic & Kidney Institute, and the study’s senior author.
The researchers analyzed microbiota from the gastrointestinal and urinary tracts of 67 individuals (43 people with no history of USD and 24 patients with active USD), and conducted a metabolomics analysis of the urinary metabolome (all small-molecule chemicals produced by cell metabolism).
Their analysis found that the urinary tract microbiota varied based on antibiotic use, family history of USD and sex—factors that have been associated with USD, but not linked to the urinary tract microbiome. The healthy and USD cohorts had significantly different urinary tract microbiota, while their gut microbiota showed only slight variation.
“The urinary tract microbiome associated with the disease much more strongly than the gut microbiome,” Dr. Miller notes. “People sometimes assume the gut microbiota is where all the action happens. While yes, that’s where the greatest density and diversity of bacteria are found, in this case, the urinary tract microbiome plays more of a role.”
Additionally, there is an intuitive relationship between the urinary tract microbiome and the progression of USD, as the urinary tract is where stones form. While this is not surprising given the proximity, there is a common misconception that the urinary tract is sterile, even though it harbors a native bacterial community.
Bacteria in protective and pathogenic contexts
Additionally, the study found that Enterobacteriaceae were more strongly associated with the USD patient group than any other bacterial family. Although not included in this investigation, previous research has shown that this family of bacteria is also associated with infection stones. Taken together, this suggests that Enterobacteriaceae plays a role in driving disease, everywhere from the gut to the urinary tract and even in the stones themselves.
Conversely, Lactobacillus were greatly reduced in the USD population, suggesting a protective, stone-prohibiting role.
While it’s understood that Enterobacteriaceae and Lactobacillus promote USD disease and protect against stone formation, respectively, it is not clear why. Dr. Miller hypothesizes that antibiotics are likely responsible for the dysbiosis associated with these bacterial families in the microbiome. Future studies will aim to elucidate the specific mechanisms related to stone development.
Next steps: predicting risk and rationalizing antibiotics
The team is now developing a longitudinal study to track the shift in the microbial environment to determine when urinary stones begin to develop and who is at greatest risk.
“We would like to build predictive assays of an individual’s microbiome to determine their likelihood of developing stones,” says Dr. Miller. This methodology would have implications for patients with recurrent episodes, family history of USD and risk for stones based on other metrics.
Importantly, the study also calls attention to the potential overuse of antibiotics.
“It demonstrates the need for clinicians to rationally prescribe antibiotics to patients. There are known—and unknown—implications that should be considered.”
The Cleveland Clinic Clinical Research Unit and Metabolomics Core helped to make this research possible.
Story adapted from Consult QD.