Forty Years of Oxalobacter formigenes, a Gutsy Oxalate-Degrading Specialist

Abstract

Oxalobacter formigenes , a unique anaerobic bacterium that relies solely on oxalate for growth, is a key oxalate-degrading bacterium in the mammalian intestinal tract. Degradation of oxalate in the gut by O. formigenes plays a critical role in preventing renal toxicity in animals that feed on oxalate-rich plants. The role of O. formigenes in reducing the risk of calcium oxalate kidney stone disease and oxalate nephropathy in humans is less clear, in part due to difficulties in culturing this organism, and the lack of studies which have utilized diets controlled in their content of oxalate. Herein, we review the literature on the 40 th anniversary of the discovery of O. formigenes , with a focus on its biology, its role in gut oxalate metabolism and calcium oxalate kidney stone disease, and potential areas of future research. Results from ongoing clinical trials utilizing O. formigenes in healthy volunteers and in patients with Primary Hyperoxaluria Type 1 (PH1), a rare but severe form of calcium oxalate kidney stone disease, will also be discussed. Information has been consolidated on O. formigenes strains and best practices to culture this bacterium, which should serve as a good resource for researchers.

New perspectives on an old grouping: The genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention

“…While we were not able to sequence the genomes of all Oxalobacter strains, the 16S rRNA gene was used to predict the species that additional strains should be assigned to. These results revealed that SOx4, OxC, and BLISS are likely O. formigenes strains; BA4 belongs to O. aliiformigenes; and OxCR6 is part of O. paeniformigenes, which has been similarly shown by others (Sidhu et al, 1997;Daniel et al, 2021). Similarly, the data suggested that strain OxCR6 is related to O. paeniformigenes, a relationship that was is supported by the comparable patterns of oxc amplification reported previously (Sidhu et al, 1997).…”

“…Together, these attributes highlight the differences in phage resistance strategies between the species, which could influence their ability to colonize an ecosystem. Given that HOxBLS (O. paraformigenes) was commonly used as a representative strain for group II (Daniel et al, 2021) (Daniel et al, 2021). Given that the oxc gene is critical for metabolism and has been used as a target for genetic identification, we investigated if these genetic differences could alter protein function.…”

“…Oxalobacter formigenes strains are described in Supplementary Table S1 and were routinely cultured in Hungate tubes as described by Hungate (1950) . Strains were grown in anaerobic oxalate broth with various amounts of oxalate added at 37°C for up to 3 days ( Daniel et al, 2021 ). The broth was modified by increasing the acetate concentration to 5 mM.…”

“…Individuals with primary hyperoxaluria have a defect in glycolate metabolism, which increases oxalate production. Although oxalate is an end product of human metabolism, humans do not possess the enzymes to metabolize oxalate ( Daniel et al, 2021 ). Instead, the molecule is either released into the intestinal lumen for fecal excretion or the renal system for urinary excretion ( Whittamore and Hatch, 2017 ).…”

Probiotics in the Prevention of the Calcium Oxalate Urolithiasis

“…However, additional analysis of the ratio of urinary oxalate excretion to urinary creatinine excretion showed a significant increase after eight weeks of treatment in the treated group compared with the placebo group. Unfortunately, even though phase II/III clinical trials showed that the 24-week treatment with Oxabact™ OC3 was safe and well-tolerated in patients with primary hyperoxaluria, no effects were noted of the treatment on urinary oxalate levels or on the ratio of urinary oxalate excretion to urinary creatinine excretion [ 67 , 68 , 69 ].…”