Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1

Abstract

Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.

Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population Health

“…Recent studies suggest a link between USD and the intestinal microbiota. For example, intestinal colonization with Oxalobacter formigenes, which degrades oxalate, is associated with lower urine oxalate levels and fewer recurrent stones (31,32), although a protective effect of exogenous Oxalobacter remains unproven (32). Advances in DNA-based sequencing may identify other bacterial communities, which will further clarify the association between stone formation and urinary or intestinal dysbiosis (Table 1).…”

Probiotics for prevention of urinary stones

“…Studies in a mouse model of type 1 PH support the possible effect of this strategy (35). Indeed, in a small unblinded pilot study of four PH patients, urine oxalate excretion fell up to 50% during 4 weeks on an oral preparation of O. formigenes (36). In this pilot study, three out of five patients with preserved renal function demonstrated a 22-48% reduction of urinary oxalate excretion while taking the first oral formulation of O. formigenes.…”

Primary and secondary hyperoxaluria: Understanding the enigma

“…This has been well documented in both human and animal experiments [36,37] . Loss of this bacterium occurs after the use of antibiotics [38] and its restoration may have a role in treatment of hyperoxaluria.…”