Microbiome alterations linked to kidney stone formation

A recent study published in Microbiome suggests that changes in the gut, urinary, and salivary microbiomes are associated with the formation of kidney stones.¹

The findings also suggested that patients with kidney stones had been exposed to more antimicrobials given their increased number of antibiotic-resistant genes.

For the study, the investigators compared the 3 microbiomes of 83 patients with kidney stones to 30 healthy controls. Patients with kidney stones had not taken antibiotics in the prior 90 days and underwent surgery to remove their stones at St. Joseph’s Health Care London in Ontario.

“Our testing – called shotgun metagenomic sequencing – allowed us to discover which bacteria were present in the gut and the genetic capabilities of those bacteria, or how it functions. We also did a simpler sequencing of the oral and urinary samples,” explained lead author Kait Al, PhD, in a news release on the findings.² Al is a postdoctoral research fellow at Western University’s Schulich School of Medicine & Dentistry in London, Ontario.

Overall, the investigators observed that health-associated markers, such as vitamin production, butyrate biosynthesis, and core beneficial taxa were displaced by virulence factors, antimicrobial resistance elements, and pathobionts in the urinary and gut microbiota of stone formers.

Urinary samples from those included in the study revealed a greater abundance of sequence variants such as Gadnerella sp., Megasphaera sp., and Alloscardovia omnicolens among healthy controls compared with stone formers, whereas Lactobacillus jensenii was more abundant in stone formers. The urinary samples from stone formers were also shown to have enhanced levels of vitamin B6 biosynthesis and significantly depleted levels of vitamin B12 biosynthesis, butyrate biosynthesis, and several basal bioenergetic enzymatic pathways compared with healthy controls.

Saliva samples from the 2 cohorts demonstrated a higher diversity in stone formers compared with healthy controls.

From the gut microbiome, 82 bacterial taxa were shown to be differentially abundant between stone formers and controls. Overall, the 2 cohorts differed in alpha diversity, relative taxonomic composition, functional potential, and overall network structure. This included an enrichment of numerous pathobionts and disease-associated microbes in stone formers, as well as decreases in unclassified taxa from the phylum Bacillota and the health-associated F. prausnitzii, according to the authors.

Other alterations with potential for stone development included the enrichment of Desulfovibrio spp., a significant signature of stone formers based on selbal analysis, and Flavonifractor plautii. Notably, the investigators did not find any significant difference in O. formigenes abundance between the 2 cohorts, showing no apparent oxalate-degrading role in stone formation. 

The findings also suggested that patients with kidney stones had been exposed to more antimicrobials given their increased number of antibiotic-resistant genes.

“We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” noted Jeremy Burton, PhD, MSc, in the news release.² Burton is the Lawson Scientist and Research Chair of human microbiome and probiotics at St. Joseph’s Health Care London and an associate professor of microbiology and immunology at Schulich Medicine & Dentistry in London, Ontario.

Although the authors note that further research is needed, they say that their findings point to the importance of maintaining a healthy microbiome.

They concluded, “If the diversity and robust functional potential of the healthy human microbiome is repeatedly assaulted by the average Westernized lifestyle via antibiotic exposure, diet, and other environmental factors, kidney stone prevalence will continue to increase. To prevent the cyclic recurrence of this disease, future management of nephrolithiasis should incorporate both the prevention of microbiome disturbance and the use of agents for subsequent restoration of homeostasis.”¹

References

1. Al KF, Joris BR, Daisley BA, et al. Multi-site microbiota alteration is a hallmark of kidney stone formation. Microbiome. 2023 Nov 25;11(1):263. doi:10.1186/s40168-023-01703-x

2. New study sheds light on the connection between the microbiome and kidney stones. News release. Lawson Health Research Institute. December 20, 2023. Accessed December 21, 2023. https://www.newswise.com/articles/new-study-sheds-light-on-the-connection-between-the-microbiome-and-kidney-stones