The Role of the Intestinal Microbiome in Oxalate Homeostasis

Abstract

Over the last 40 years, there has been a doubling in the prevalence of urinary stone disease (USD), representing a broad shift in public health. Nearly 80% of uroliths are comprised primarily of calcium oxalate. Oxalate, an organic acid commonly found in plant-based foods and produced endogenously as a terminal metabolite in the liver, is in part metabolized by bacteria in the gut. Remaining oxalate can be excreted as waste through the gastrointestinal or urinary tracts. In the urinary tract, oxalate can bind to calcium and aggregate into stones. Thus, to effectively prevent recurrent episodes of calcium oxalate stone formation, it is vital to understand how the intestinal microbiome maintains oxalate homeostasis and low levels of oxalate excretion. While much of the work has focused on the role of the intestinal bacterium, Oxalobacter formigenes, an oxalate-degrading specialist, recent metagenomic studies show that oxalate homeostasis is maintained more by a symbiotic community of bacteria rather than isolated species. Here we provide an overview of oxalate homeostasis by the intestinal microbiome, how this function can be disrupted, and its relevance for USD.