Researchers have discovered conclusive evidence of a kidney microbiome that affects kidney health and the formation of kidney stones, showing that the urinary tract is not free of bacteria and that low bacterial levels are normal. The article outlines the thorough, multi-faceted approach taken by a team to identify and analyze this small community of bacteria, utilizing studies conducted in preclinical settings, human subjects, and laboratory settings.
Cleveland Clinic researchers have discovered definitive evidence of a kidney microbiome that impacts kidney health and the formation of kidney stones, indicating that the urinary tract is not completely sterile and that low levels of bacteria are standard.
The Nature Communications article outlines the comprehensive approach utilized by a team led by Aaron Miller, PhD, and José Agudelo, MD, to identify and analyze the small bacterial community through a combination of preclinical experiments, human studies, and laboratory research.
The researchers also pinpointed specific bacteria within the microbiome that may either encourage or inhibit kidney stone formation. Additionally, they found that the misuse of antibiotics (often linked to the development of kidney stones in hospital environments) resulted in a microbiome shift towards bacteria that promote stone formation.
Dr. Miller is optimistic that the team’s findings will challenge the outdated belief in a sterile urinary tract and pave the way for improved preventive measures and treatments for a condition that has seen minimal medical advancements in over thirty years.
“Urologic conditions such as kidney stones affect 63% of adults and are becoming more common,” he states. “The data consistently supports a bacterial link. Without moving past the notion of sterility, we cannot develop better treatments or prevention strategies.”
Normally, the level of bacteria in urine is low, but it’s rarely absent. Nevertheless, the urobiome—the microbiome of various organs in the urinary tract, including the kidneys and bladder—has been a contentious topic since it was first observed in human urine less than 15 years ago.
The study’s lead author and urologist, José Agudelo, MD, with considerable experience in urinary stone disease, notes that earlier indirect evidence for a kidney microbiome provided convincing insights but left room for skepticism.
For a bacterial community to qualify as a true microbiome, it must meet three criteria: stability, consistency, and reproducibility, as well as being metabolically active. The team’s research demonstrated each of these characteristics in the bacteria located within the urinary tract. Additionally, they found that the presence of these bacteria was not solely due to disease, as they identified them in individuals without any signs of urologic issues.
Prior research indicated that two specific species identified by Drs. Miller and Agudelo, E. coli and Lactobacillus crispatus, were linked with the presence and absence of kidney stones, respectively. The researchers investigated whether the metabolic activity of this newly discovered microbial community contributed to kidney stone formation.
To test if the kidney microbiome affected stone formation, the researchers cultured bacteria in a specialized chamber that simulates urine movement within the kidneys. They then introduced components of kidney stones, such as oxalate and calcium, to observe the outcomes.
Several large, kidney stone-like crystal formations emerged in the chambers with E. coli. Chemical and X-ray analyses indicated these structures were indistinguishable from actual human kidney stones. In contrast, no stones formed in the chambers with Lactobacillus. When both bacteria were cultured together, they formed very small crystal structures that were chemically and structurally distinct from kidney stones, indicating that Lactobacillus somehow inhibits E. coli’s capability to produce kidney stones.
In their preclinical models, the team also observed that excessive antibiotic use disrupted the balance of the kidney microbiome, shifting it from the beneficial Lactobacillus to the stone-forming E. coli. They believe that, collectively, their findings could clarify why individuals undergoing long-term antibiotic treatments have a higher likelihood of developing kidney stones.
Dr. Agudelo states that their findings imply that different bacteria generate molecules that either promote or prevent kidney stone formation, which he aims to utilize in developing new therapeutic and diagnostic strategies. He is already exploring which bacterial metabolites affect stone development and how they do so.
“If the kidney microbiome can have an effect on kidney stones, it likely influences other kidney-related diseases too,” Dr. Miller observes. “We are actively studying microbial signatures for various kidney diseases and have even submitted a grant to examine how certain genetic variations impact the renal microbiome and the risk of kidney diseases among different ethnic groups.”
