Manipulating Oxalate Decarboxylase Provides the Basis of Antilithic Therapy by Acting on the Gut Microbiota

Abstract

A high concentration of oxalate is associated with an increased risk of kidney calcium oxalate (CaOx) stones, and the degradation of exogenous oxalate mainly depends on oxalate-degrading enzymes from the intestinal microbiome. We found that Zinc Gluconate supplement to patients with CaOx kidney stones could significantly improve the abundance of oxalate metabolizing bacteria in human body through clinical experiments on the premise of simultaneous antibiotic treatment and the imbalance of Lactobacillus and OxDC was involved in CaOx kidney stones through clinical sample analysis. Then, we identified that Zn2+ could be used as an external factor to improve the activity of OxDC and protect Lactobacillus, achieved the preventive effect on rats with stones aggravated by antibiotics. Finally, by analyzing the three-dimensional structure of OxDC and some in vitro experiments, we propose a hypothesis Zn2+ increases the metabolism of oxalate in humans through its positive effects on Lactobacillus and OxDC to reduce CaOx kidney stone symptoms in rats. IMPORTANCEUrinary stone disease is one of the most common urological disorders, and 70%-80% of urinary stones are calcium oxalate (CaOx) stones. We found the structural basis and metabolic mechanism by which oxalate decarboxylase metabolizes oxalate were elucidated, and Zn2+ was illustrated to have therapeutic effects on CaOx stones by improving the tolerance of Lactobacillus to antibiotics. According to that, proper Zn2+ levels in the diet, the consumption of more probiotic food and avoidance of the antibiotic overuse might be desirable measures for the prevention and treatment of kidney stones. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/512337v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@d3df85org.highwire.dtl.DTLVardef@1f7b3f5org.highwire.dtl.DTLVardef@147d861org.highwire.dtl.DTLVardef@1cf046e_HPS_FORMAT_FIGEXP M_FIG C_FIG