Animal and human studies have provided compelling evidence that colonization of the intestine with Oxalobacter formigenes reduces urinary oxalate excretion and lowers the risk of forming calcium oxalate kidney stones. The mechanism providing protection appears to be related to the unique ability of O. formigenes to rely on oxalate as a major source of carbon and energy for growth. However, much is not known about the factors that influence colonization and host-bacterium interactions. We have colonized mice with O. formigenes OxCC13 and systematically investigated the impacts of diets with different levels of calcium and oxalate on O. formigenes intestinal densities and urinary and intestinal oxalate levels. Measurement of intestinal oxalate levels in mice colonized or not colonized with O. formigenes demonstrated the highly efficient degradation of soluble oxalate by O. formigenes relative to other microbiota. The ratio of calcium to oxalate in diets was important in determining colonization densities and conditions where urinary oxalate and fecal oxalate excretion were modified, and the results were consistent with those from studies we have performed with colonized and noncolonized humans. The use of low-oxalate purified diets showed that 80% of animals retained O. formigenes colonization after a 1-week dietary oxalate deprivation. Animals not colonized with O. formigenes excreted two times more oxalate in feces than they had ingested. This nondietary source of oxalate may play an important role in the survival of O. formigenes during periods of dietary oxalate deprivation. These studies suggest that the mouse will be a useful model to further characterize interactions between O. formigenes and the host and factors that impact colonization.
Oxalobacter formigenes is a Gram-negative, obligate anaerobic bacterium that requires oxalate as a carbon source for energy and growth (1). O. formigenes is part of the microbiota in the large intestine of many humans and other mammalian species (1-6). A review of colonization frequencies conducted worldwide indicated that 38% to 77% of a normal population is colonized with O. formigenes (7). Recent evidence suggests that a lack of colonization with this oxalate-degrading specialist is a risk factor for idiopathic recurrent calcium oxalate kidney stone disease (8,9). Controlled diet studies in healthy human subjects have also indicated that O. formigenes-colonized individuals excrete significantly less oxalate in 24-hour urine collections when they consume diets containing moderate oxalate (250 mg) and low calcium (400 mg) levels (10).Little is known about how and when individuals become colonized or how O. formigenes persists over time. Studies to date suggest it occurs early in childhood (11), and if animal experiments provide any insight, it is obtained from the environment, not directly from the mother (12). Several studies have indicated that the intake of antibiotics can result in the loss of colonization (7,(13)(14)(15), and this is supported by decreased prevalence...