Effect of Oral Administration of Metronidazole or Prednisolone on Fecal Microbiota in Dogs

Abstract

Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14), and 14 and 28 days after cessation (day 28 and 42). DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA) gene sequences using next-generation sequencing (Illumina MiSeq). In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health; however, further investigations into the effects on diseased dogs are needed.

High-Throughput Sequencing of Microbial Community Diversity and Dynamics during Douchi Fermentation

“…All 250 bp pair-end sequence reads were connected using COPE software (Connecting Overlapped Pair-end, V 1.2.1) [27] to merge read pairs into tags from DNA fragments. Further data processing was performed as previously described [28–32,18] and included removal of sequencing noise using the pre.cluster tool in the MOTHUR software package v. 1.31.2 [33], and de novo chimera detection and removal in UCHIME v. 4.2. Operational taxonomic units (OTUs) were also determined using MOTHUR, with a 97% sequence identity threshold [33].…”

The Gastrointestinal Microbiome: A Review

“…Metronidazole is a nitroimidazole antibiotic and antiprotozoal that is commonly used in small animals with acute and chronic gastrointestinal disorders. A recent study in healthy dogs revealed that metronidazole decreases fecal bacterial diversity but increases the proportions of putatively beneficial bacteria such as Bifidobacterium . Tylosin is a macrolide antibiotic that is typically used to treat chronic enteropathies in dogs, especially a variant of antibiotic‐responsive diarrhea termed tylosin‐responsive diarrhea (TRD).…”

Proposal for rational antibacterial use in the diagnosis and treatment of dogs with chronic diarrhoea

“…(Manchester et al 2019). Faecal bacterial diversity was also reduced when administering oral metronidazole for 14 days (12.5 mg/kg BID) to healthy dogs (Igarashi et al 2014). Similarly, oral administration of amoxicillin (10 mg/kg BID for 7 days) to healthy dogs resulted in differences in faecal bacterial composition before and after administration, with many faecal E. coli isolates showing increased resistance to multiple ABs during and after treatment (Grønvold et al 2010).…”