Open AccessEffects of metronidazole on the fecal microbiome and metabolome in healthy dogs
Author(s) -
Pilla Rachel,
Gaschen Frederic P.,
Barr James W.,
Olson Erin,
Honneffer Julia,
Guard Blake C.,
Blake Amanda B.,
Villanueva Dean,
Khattab Mohammad R.,
AlShawaqfeh Mustafa K.,
Lidbury Jonathan A.,
Steiner Jörg M.,
Suchodolski Jan S.
Publication year - 2020
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.15871
Subject(s) - metabolome , metronidazole , microbiome , dysbiosis , feces , medicine , physiology , deoxycholic acid , antibiotics , microbiology and biotechnology , gastroenterology , gut flora , pharmacology , bile acid , metabolite , biology , immunology , bioinformatics
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.