Abstract: Background – Metabolic dysfunction secondary to high-fat diet consumption may seriously diminish quality of life and shorten the lifespan in dogs and humans, alike. Diets high in fat increase the secretion of bile acids (BA), promote microbial imbalances, and drive chronic intestinal inflammation. Hypothesis - A high-fat, low-fiber Western diet (WD) fed to healthy, non-obese dogs disrupts BA metabolism and promotes microbial imbalances, altered apoptosis, and pro-carcinogenic inflammation. Animals – Eight healthy, laboratory-reared, Beagle dogs. Methods – A dietary trial compared the effects of a control diet (CD) formulated on recommended maintenance macronutrient and fiber levels to a high-fat, high-monosaccharide, and low-fiber WD. The study had three consecutive feeding periods: (1) five weeks of CD, followed by (2) seven weeks of WD and (3) four weeks of CD (recovery). Outcome measures included molecular/microbiologic testing of colonic biopsies, intestinal histopathology, and fecal BAs at the completion of each feeding period. Statistical analysis was performed using one-way ANOVA with significance defined as p < 0.05. Results – Physiological parameters suggestive of metabolic dysfunction were observed in dogs fed WD. Cell markers of apoptosis (TUNEL) and inflammation (NF-ĸB) as well as serum high-sensitivity C-reactive protein were increased (p < 0.05) in dogs fed WD vs. CD. Other perturbations seen with WD ingestion included altered (p < 0.05) mucosal populations of Bacteroides, Clostridia, and Enterobacteriaceae and increased (p < 0.05) levels of fecal cholic acid and serum myeloperoxidase. Conclusions: High-fat diet fed to healthy dogs promotes microbial imbalances, disturbed host metabolism, and pro-carcinogenic inflammation.