Alterations along the gut-urinary axis in dogs with calcium oxalate urolithiasis
摘要
Calcium oxalate (CaOx) is a common type of urinary stone affecting humans and animals. Mechanisms underlying CaOx stone formation are incompletely understood, but growing evidence has linked disturbances in the gut and urinary microbiomes to stone formation. Dogs naturally develop CaOx stones and represent a powerful translational model for studying microbiome-stone interactions. In this study, fecal and urine samples were collected from 20 dogs with CaOx urolithiasis and 20 age-, breed-, and sex-matched controls. Gut and urinary microbiota were profiled using 16 S rRNA sequencing and urinary metabolomics using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Dogs with CaOx stones exhibited reduced gut microbial diversity, including deficiencies in bacteria associated with short chain fatty acid and bile acid metabolism, such as Peptacetobacter hiranonis (q-value < 0.05). Urinary microbiota and metabolomic profiles markedly differed between groups. Stone formers had higher abundances of Lachnoclostridium, Fusobacterium, and Pseudomonas (q-values < 0.05) and lower abundances of 4’-hydroxypropiophenone sulfate and N, N-dimethyl-5-aminovalerate (q-values < 0.01). Overall dietary protein and fiber intake were similar between groups (P > 0.05). However, the majority of dogs with stones consumed therapeutic stone prevention diets, whereas controls consumed a wider variety of diets, representing an important potential confounding factor. Together, these findings provide new insights into disturbances in gut and urinary microbial and metabolomic profiles in a canine model of CaOx urolithiasis.