Chapter 17 - Recombinant Lactic Acid Bacteria Secreting OxdC as a Novel Therapeutic Tool for the Prevention of Kidney Stone Disease

Abstract

Kidney stone disease is a dreadful pathological condition, and affects 20% of the population worldwide. The majority of renal stones contain calcium oxalate, and oxalate has vital role in the pathogenesis of renal stone. Humans derive oxalate from endogenous production and increased intake of dietary oxalate. Elevated oxalate levels lead to hyperoxaluria, a major risk factor for recurrent nephrolithiasis. Current treatment options in patients with primary and secondary hyperoxaluria are inadequate, and do not always lead to significant reduction in urinary oxalate excretion. Manipulation of gut flora with the potential probiotic bacteria may have a positive impact on gut oxalate levels, and may decrease oxalate absorption. Several reports documented gut microbes capable to degrade luminal oxalate, and reduce the risk of hyperoxaluria. In addition, the oxalate decarboxylase gene from Bacillus subtilis degrades oxalate into CO2 and formate, and studies have proven that administration of recombinant lactic acid bacteria (LAB) expressing oxalate decarboxylase (OxdC) decreased urinary oxalate excretion, and prevented calcium oxalate stone formation. Thus, potential oxalate degrading probiotic recombinant LAB expressing heterologous oxalate decarboxylase could be beneficial to mitigate hyperoxaluria efficiently by intestinal degradation of dietary oxalate.