Response of Germfree Mice to Colonization by Oxalobacter formigenes and Altered Schaedler Flora
ABSTRACTColonization withOxalobacter formigenesmay reduce the risk of calcium oxalate kidney stone disease. To improve our limited understanding of host-O. formigenesand microbe-O. formigenesinteractions, germfree mice and mice with altered Schaedler flora (ASF) were colonized withO. formigenes. Germfree mice were stably colonized withO. formigenes, which suggests thatO. formigenesdoes not require other organisms to sustain its survival. Examination of intestinal material indicated no viableO. formigenesin the small intestine and ∼4 × 106CFUO. formigenesper 100 mg contents in the cecum and proximal colon, with ∼0.02% of total cecalO. formigenescells being tightly associated with the mucosa.O. formigenesdid not alter the overall microbial composition of ASF, and ASF did not affect the capacity ofO. formigenesto degrade dietary oxalate in the cecum. Twenty-four-hour collections of urine and feces in metabolic cages in semirigid isolators demonstrated that the introduction of ASF into germfree mice significantly reduced urinary oxalate excretion. These experiments also showed thatO. formigenes-monocolonized mice excreted significantly more urinary calcium than did germfree mice, which may be due to degradation of calcium oxalate crystals byO. formigenesand subsequent intestinal absorption of free calcium. In conclusion, the successful establishment of mouse models with defined flora andO. formigenesshould improve our understanding ofO. formigenes-host andO. formigenes-microbe interactions. These data support the use ofO. formigenesas a probiotic that has limited impact on the composition of the resident microbiota but provides an efficient oxalate-degrading function.IMPORTANCEDespite evidence suggesting that a lack ofOxalobacter formigenescolonization is a risk factor for calcium oxalate stone formation, little is known aboutO. formigenesbiology. This study is the first to utilize germfree mice to examine the response to monocolonization withO. formigenes, as well as the impact of a defined bacterial cocktail (i.e., ASF) onO. formigenescolonization. This study demonstrated that germfree mice receiving their regular diet remained monocolonized withO. formigenes, and it suggests that further studies withO. formigenesgnotobiotic mouse models could improve our understanding ofO. formigenesbiology and host-O. formigenesand microbe-O. formigenesinteractions.