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Response of Germfree Mice to Colonization by Oxalobacter formigenes and Altered Schaedler Flora

2016; American Society for Microbiology; Volume: 82; Issue: 23 Linguagem: Inglês

10.1128/aem.02381-16

1098-5336

Xingsheng Li, Melissa L. Ellis, Alexander E. Dowell, Ranjit Kumar, Casey D. Morrow, Trenton R. Schoeb, John Knight,

Pelvic floor disorders treatments

ABSTRACT Colonization with Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stone disease. To improve our limited understanding of host- O. formigenes and microbe- O. formigenes interactions, germfree mice and mice with altered Schaedler flora (ASF) were colonized with O. formigenes . Germfree mice were stably colonized with O. formigenes , which suggests that O. formigenes does not require other organisms to sustain its survival. Examination of intestinal material indicated no viable O. formigenes in the small intestine and ∼4 × 10 6 CFU O. formigenes per 100 mg contents in the cecum and proximal colon, with ∼0.02% of total cecal O. formigenes cells being tightly associated with the mucosa. O. formigenes did not alter the overall microbial composition of ASF, and ASF did not affect the capacity of O. formigenes to 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 that O. formigenes -monocolonized mice excreted significantly more urinary calcium than did germfree mice, which may be due to degradation of calcium oxalate crystals by O. formigenes and subsequent intestinal absorption of free calcium. In conclusion, the successful establishment of mouse models with defined flora and O. formigenes should improve our understanding of O. formigenes -host and O. formigenes -microbe interactions. These data support the use of O. formigenes as a probiotic that has limited impact on the composition of the resident microbiota but provides an efficient oxalate-degrading function. IMPORTANCE Despite evidence suggesting that a lack of Oxalobacter formigenes colonization is a risk factor for calcium oxalate stone formation, little is known about O. formigenes biology. This study is the first to utilize germfree mice to examine the response to monocolonization with O. formigenes , as well as the impact of a defined bacterial cocktail (i.e., ASF) on O. formigenes colonization. This study demonstrated that germfree mice receiving their regular diet remained monocolonized with O. formigenes , and it suggests that further studies with O. formigenes gnotobiotic mouse models could improve our understanding of O. formigenes biology and host- O. formigenes and microbe- O. formigenes interactions.