PSVIII-4 Changes in microbial metabolic pathways are associated with history of calcium oxalate stone formation in a national survey of older dogs.

Abstract Calcium oxalate urinary and/or bladder uroliths (stones) commonly occur, and re-occur, in dogs. A cross-sectional study of client-owned dogs aged ≥ 5 yrs (mean 9.3 yrs, n=487) was conducted in US veterinary clinics from 2016-2017. Results from clinical exams including blood CBC and chemistry, dietary history, and gastrointestinal (GI) microbiome analysis were compared between dogs with a history of calcium oxalate stones (CaOx, n=40) and generally healthy dogs (H, n=447). Among CaOx, 21 (53%) were fed a therapeutic food specific for the management of CaOx stones (CaOx-TF), 19 (47%) were not (CaOx-NTF). Within CaOx-TF, 7 were fed Hill’s Prescription Diet c/d Multicare, a therapeutic food intended to manage CaOx stones (CaOx-HTF). Fecal microbiome analysis was performed using Illumina HiSeq shotgun metagenomics sequencing technology with a target depth of 6M reads/sample. Results were processed using the CosmosID (Germantown, MD, USA) proprietary database and bioinformatics workflow yielding microbial abundance and functional data. Statistical analysis was performed using JMP Pro v1. PCA analysis revealed that the microbial metabolic functional capacity (PC1 35.0%; PC2 6.4%) explained more variability between CaOx vs. H than microbial species abundance (PC1 12.8%; PC2 8.8%). Linear mixed model regression analyses revealed five metabolic pathways of interest were increased in CaOx vs. H, including phylloquinol (vitamin K1) biosynthesis, menaquinol (vitamin K2) biosynthesis, arginine biosynthesis, ubiquinol biosynthesis, allantoin degradation, and oxalate degradation, while a sixth pathway (branched chain amino acids biosynthesis) was decreased (FDR adj p< 0.05 for all). PCA reanalysis using only components of the six pathways explained 79.7% of the total variability between CaOx vs. H (PC1 74.1%; PC2 5.6%). The abundance levels for these six pathways showed similar though non-significant patterns when comparing CaOx-HTF dogs vs. CaOx-NTF and H. The abundance of a microbial oxalate degradation enzyme (oxalyl-coA-decarboxylase, EC 4.1.1.8) was higher in CaOx-HTF vs. CaOx-NTF or H dogs (adj p< 0.05). Finally, values for circulating BUN and BUN/creatinine ratio were significantly lower in H vs. CaOx-NTF; CaOx-HTF dogs appeared more similar to H, though they did not differ statistically from either group. Overall, this study highlights the potential to use GI microbial metabolic parameters as biomarkers to differentiate CaOx vs. H dogs as well the potential for therapeutic foods to help manage CaOx stone formation via modulation of GI microbiome functions. This study was reviewed & approved by the Institutional Animal Care & Use Committee at Hill’s Pet Nutrition, and was funded by Hill’s Pet Nutrition, Inc.