Effects of metronidazole on the fecal microbiome and metabolome 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 < .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).

Effect of sequentially fed high protein, hydrolysed protein, and high fibre diets on the faecal microbiota of healthy dogs: a cross-over study

“…Recent studies evaluating the effect of a hypoallergenic diet on the gut microbiome in healthy dogs and in dogs with food-responsive enteropathy showed that the impact of the diet was minimal in the microbial composition as well as in the metabolome [16,37]. In these studies, dogs were fed with commercial maintenance diets before the introduction of the new diet, whereas in our study the baseline diet was meat-based, which could potentially have an in uence on the results.…”

“…Hydrolysed diets are associated with bene cial changes in the intestinal microbiota and clinical signs of dogs with chronic enteropathies [35]. However, to our knowledge, there is no published data on how hypoallergenic or hydrolysed diets affect the gastrointestinal microbiome in healthy dogs fed different types of diets prior to the change and in turn, which component of the diet is having the most impact [16,36,37]. The modern pet food industry uses several bre sources (mainly by-products derived from the processing of grains, fruits and vegetables) in the formation of diets for dogs [15,38].…”

Diagnostic value of fecal cultures in dogs with chronic diarrhea

“…In the colon, primary bile acids are converted to secondary bile acids. The main converter of bile acids in dogs is C. hiranonis 18,20,26 . Decreased abundance of C. hiranonis leads to lack of conversion of primary to secondary bile acids, which is associated with an increased DI 10,18,20,26 .…”

“…18,20,26 Decreased abundance of C. hiranonis leads to lack of conversion of primary to secondary bile acids, which is associated with an increased DI. 10,18,20,26 Decreased numbers of C. hiranonis also were associated with a lower fecal concentration of secondary bile acids and with an increased abundance of E. coli. [36][37][38] However because of sequencing techniques, it is known that strictly anaerobic bacteria predominate in the intestinal microbiota.…”

Best Practices for Microbiome Study Design in Companion Animal Research

“…While these interventions should be considered in recruitment as well (see "Recruitment"), it is important to account for and understand how other interventions may affect the study outcome. For example, non-study-related antibiotics should be avoided during microbiome studies and for at least several weeks prior to the beginning of a study because microbiota do not completely recover within this timeframe (80,81). Several other common medications including antiparasitics (82) and proton pump inhibitors (83,84) can also affect the microbiota and their use should be avoided where possible, or at least recorded.…”