How metronidazole changes gut bacteria and metabolism in healthy dogs

Abstract

BACKGROUND: Metronidazole has a substantial impact on the gut microbiome. However, the recovery of the microbiome after discontinuation of administration, and the metabolic consequences of such alterations have not been investigated to date. OBJECTIVES: To describe the impact of 14-day metronidazole administration, alone or in combination with a hydrolyzed protein diet, on fecal microbiome, metabolome, bile acids (BAs), and lactate production, and on serum metabolome in healthy dogs. ANIMALS: Twenty-four healthy pet dogs. METHODS: Prospective, nonrandomized controlled study. Dogs fed various commercial diets were divided in 3 groups: control group (no intervention, G1); group receiving hydrolyzed protein diet, followed by metronidazole administration (G2); and group receiving metronidazole only (G3). Microbiome composition was evaluated with sequencing of 16S rRNA genes and quantitative polymerase chain reaction (qPCR)-based dysbiosis index. Untargeted metabolomics analysis of fecal and serum samples was performed, followed by targeted assays for fecal BAs and lactate. RESULTS: No changes were observed in G1, or G2 during diet change. Metronidazole significantly changed microbiome composition in G2 and G3, including decreases in richness (P&#x2009;<&#x2009;.001) and in key bacteria such as Fusobacteria (q&#x2009;<&#x2009;0.001) that did not fully resolve 4&#x2009;weeks after metronidazole discontinuation. Fecal dysbiosis index was significantly increased (P&#x2009;<&#x2009;.001). Those changes were accompanied by increased fecal total lactate (P&#x2009;<&#x2009;.001), and decreased secondary BAs deoxycholic acid and lithocholic acid (P&#x2009;<&#x2009;.001). CONCLUSION AND CLINICAL IMPORTANCE: Our results indicate a minimum 4-week effect of metronidazole on fecal microbiome and metabolome, supporting a cautious approach to prescription of metronidazole in dogs.