title: Characterization of microbial dysbiosis and metabolomic changes in dogs with acute diarrhea.
abstract: Limited information is available regarding the metabolic consequences of intestinal dysbiosis in dogs with acute onset of diarrhea. The aim of this study was to evaluate the fecal microbiome, fecal concentrations of short-chain fatty acids (SCFAs), as well as serum and urine metabolites in healthy dogs (n=13) and dogs with acute diarrhea (n=13). The fecal microbiome, SCFAs, and serum/urine metabolite profiles were characterized by 454-pyrosequencing of the 16S rRNA genes, GC/MS, and untargeted and targeted metabolomics approach using UPLC/MS and HPLC/MS, respectively. Significantly lower bacterial diversity was observed in dogs with acute diarrhea in regards to species richness, chao1, and Shannon index (p=0.0218, 0.0176, and 0.0033; respectively). Dogs with acute diarrhea had significantly different microbial communities compared to healthy dogs (unweighted Unifrac distances, ANOSIM p=0.0040). While Bacteroidetes, Faecalibacterium, and an unclassified genus within Ruminococcaceae were underrepresented, the genus Clostridium was overrepresented in dogs with acute diarrhea. Concentrations of fecal propionic acid were significantly decreased in acute diarrhea (p=0.0033), and were correlated to a decrease in Faecalibacterium (ρ=0.6725, p=0.0332). The predicted functional gene content of the microbiome (PICRUSt) revealed overrepresentations of genes for transposase enzymes as well as methyl accepting chemotaxis proteins in acute diarrhea. Serum concentrations of kynurenic acid and urine concentrations of 2-methyl-1H-indole and 5-Methoxy-1H-indole-3-carbaldehyde were significantly decreased in acute diarrhea (p=0.0048, 0.0185, and 0.0330, respectively). These results demonstrate that the fecal dysbiosis present in acute diarrhea is associated with altered systemic metabolic states.
authors.affiliation: Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Blake C
authors.initials: BC
authors.lastname: Guard
authors.affiliation: Emergency and Critical Care, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
authors.forename: James W
authors.initials: JW
authors.lastname: Barr
authors.affiliation: Department of Plant Science, Penn State University, University Park, Pennsylvania, United States of America.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Reddivari
authors.affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Cory
authors.initials: C
authors.lastname: Klemashevich
authors.affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas, United States of America; Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College Station, Texas, United States of America.
authors.forename: Arul
authors.initials: A
authors.lastname: Jayaraman
authors.affiliation: Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Jörg M
authors.initials: JM
authors.lastname: Steiner
authors.affiliation: Department of Food Science, Penn State University, University Park, Pennsylvania, United States of America; The Penn State Hershey Cancer Institute, Hershey, Pennsylvania, United States of America.
authors.forename: Jairam
authors.initials: J
authors.lastname: Vanamala
authors.affiliation: Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Jan S
authors.initials: JS
authors.lastname: Suchodolski
mesh_terms: D000818:Animals; D003967:Diarrhea / Q000382:microbiology / Q000662:veterinary*; D004283:Dog Diseases / Q000382:microbiology*; D004285:Dogs; D064806:Dysbiosis / Q000382:microbiology / Q000662:veterinary*; D005243:Feces / Q000382:microbiology; D005260:Female; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D064307:Microbiota