Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs

J Vet Intern Med. 2020 Sep;34(5):1853-1866. doi: 10.1111/jvim.15871. Epub 2020 Aug 28.


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 < .001) and in key bacteria such as Fusobacteria (q < 0.001) that did not fully resolve 4 weeks after metronidazole discontinuation. Fecal dysbiosis index was significantly increased (P < .001). Those changes were accompanied by increased fecal total lactate (P < .001), and decreased secondary BAs deoxycholic acid and lithocholic acid (P < .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.

Keywords: antibiotic; bile acid metabolism; dysbiosis; fecal metabolome; microbiota; serum metabolome.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

  • Animals
  • Dogs
  • Feces
  • Metabolome*
  • Metronidazole / pharmacology
  • Microbiota*
  • Prospective Studies
  • RNA, Ribosomal, 16S / genetics


  • RNA, Ribosomal, 16S
  • Metronidazole