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.

Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs / R. Pilla, F.P. Gaschen, J.W. Barr, E. Olson, J. Honneffer, B.C. Guard, A.B. Blake, D. Villanueva, M.R. Khattab, M.K. Alshawaqfeh, J.A. Lidbury, J.M. Steiner, J.S. Suchodolski. - In: JOURNAL OF VETERINARY INTERNAL MEDICINE. - ISSN 0891-6640. - 34:5(2020 Sep), pp. 1853-1866. [10.1111/jvim.15871]

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

R. Pilla
Primo
;
2020

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 <.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.
antibiotic; bile acid metabolism; dysbiosis; fecal metabolome; microbiota; serum metabolome
Settore VET/05 - Malattie Infettive degli Animali Domestici
set-2020
28-ago-2020
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1044431
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