Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease

Gut Microbes. 2015;6(1):33-47. doi: 10.1080/19490976.2014.997612. Epub 2015 Jan 7.

Abstract

Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy.

Keywords: 16 S rRNA, 16 S ribosomal RNA; ANOSIM, analysis of similarities; CIBDAI, canine IBD activity index; FDR, false discovery rate; Faecalibacterium; GC-TOF/MS, gas chromatography coupled with time-of-flight mass spectrometry; GI, gastrointestinal; IBD; IBD, idiopathic inflammatory bowel disease; KEGG, Kyoto Encyclopedia of Genes and Genomes; LEfSe, linear discriminant analysis (LDA) effect size; PCA, principal component analysis; PCoA, principal coordinates analysis; PICRUSt, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; ROC, receiver operating characteristic; dog; dysbiosis; feces; metabolomics; microbiome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biota*
  • Dog Diseases / pathology*
  • Dog Diseases / therapy
  • Dogs
  • Feces / microbiology*
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / therapy
  • Inflammatory Bowel Diseases / veterinary*
  • Metabolome
  • Metabolomics
  • Metagenomics
  • Sequence Analysis, DNA
  • Serum / chemistry*