Metabolomic and Lipidomic Characterization of Oxalobacter formigenes to Define Intestinal Oxalate Secretion

Abstract

Kidney stone disease afflicts 1 in 11 people in the U.S. and burdens the economy with an annual treatment cost of over $10 billion. Nearly 80% of kidney stones are composed of calcium oxalate (CaOx) and form when humans are exposed to oxalate through the diet and endogenous glyoxylate metabolism in the liver. Recently, significant clinical interest has turned to the intestinal microbiome, specifically a class of “oxalotrophic” bacteria that degrade dietary oxalate in the intestine. These bacteria reduce the amount of oxalate absorbed by the body, lowering circulating and urinary oxalate, both which directly influence CaOx stone formation. One species in particular, Oxalobacter formigenes (Oxf), solely utilizes oxalate as an energy source and has the unique ability among oxalotrophs to transport endogenous oxalate from the bloodstream into the intestine to increase oxalate availability, allowing it to feed on both metabolic and dietary oxalate. The potential for Oxf as a probiotic therapy for kidney stone disease is currently being evaluated by numerous institutions. Compelling evidence demonstrates that Oxf produces some form of secreted bioactive compound to regulate oxalate transport proteins in the intestinal wall to bring oxalate across the epithelium. This compound, if identified, could potentially serve as a future therapy for kidney stone formation. This study seeks to identify this secreted factor through an Ultra High Performance Liquid Chromatography‐Mass Spectrometry‐based characterization and comparison of the metabolome and lipidome of Oxf with other oxalotrophs that cannot initiate oxalate secretion, the rationale being that the bioactive compound(s) responsible for this function should be uniquely expressed by Oxf. We also present the first characterization of the Oxf metabolome and lipidome by comparing the human strain HC1 and the wild rat strain OxWR, both which have been shown to induce net intestinal oxalate secretion across native intestinal epithelial tissue. It is essential to elucidate the molecular nature of the Oxf‐host relationship to bring this bacterium and its metabolic products to the clinic as a novel approach to kidney stone disease.Support or Funding InformationThis work was funded by the National Institutes of Health grant 2R01DK088892‐05A1.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.