Every year, approximately one million cases of kidney stone disease are diagnosed in the United States costing about $2 billion in health care. The most common stone is comprised of calcium oxalate (about 80%) and a major risk factor is elevated urinary oxalate concentration. Urinary oxalate is derived directly from food or from metabolic processes and currently there is no pharmacological treatment for reducing hyperoxaluria. The studies proposed here focus on the novel concept of reducing urinary oxalate by innocuously excreting this compound through the intestine where it can be degraded by substrate-specific bacteria (Oxalobacter sp.), present in some, but not all individuals. The specific aims address the hypothesis that Oxalobacter can locally modulate oxalate transport and enhance intestinal elimination. An integral part of the study will examine the effectiveness of Oxalobacter in reducing urinary oxalate under conditions where dietary Ca2+ is manipulated. By developing a more complete understanding of the dynamic interaction between the capacity of the intestinal mucosal barrier to secrete and excrete oxalate coupled with the ability of Oxalobacter sp. To lower intraluminal oxalate activity a novel treatment plan will emerge. The aim is to specifically direct the development of a supplementation therapy which will maximally enhance enteric oxalate excretion and reduce hyperoxaluria. PROPOSED COMMERCIAL APPLICATION: The development of an effective supplementation therapy for the control of hyperoxaluric conditions is timely. Currently, there are 1 million patients with kidney stone disease and there are patients with other oxalate-associated diseases, including primary hyperoxaluria which invariably results in death at an early age due to oxalate-induced kidney failure. The potential for the clinical application of a novel treatment strategy to reduce urinary oxalate excretion is broad-based and highly significant.