Untargeted Analysis of Serum Metabolomes in Dogs with Exocrine Pancreatic Insufficiency

Patrick C. Barko, Stanley I. Rubin, Kelly S. Swanson, Maureen A. McMichael, Marcella D. Ridgway, David A. Williams

Research output: Contribution to journalArticlepeer-review


Exocrine pancreatic insufficiency (EPI) is a malabsorptive syndrome resulting from insufficient secretion of pancreatic digestive enzymes. EPI is treated with pancreatic enzyme replacement therapy (PERT), but the persistence of clinical signs, especially diarrhea, is common after treatment. We used untargeted metabolomics of serum to identify metabolic disturbances associated with EPI and generate novel hypotheses related to its pathophysiology. Fasted serum samples were collected from dogs with EPI (n = 20) and healthy controls (n = 10), all receiving PERT. Serum metabolomes were generated using UPLC-MS/MS, and differences in relative metabolite abundances were compared between the groups. Of the 759 serum metabolites detected, 114 varied significantly (p < 0.05, q < 0.2) between dogs with EPI and healthy controls. Differences in amino acids (arginate, homoarginine, 2-oxoarginine, N-acetyl-cadaverine, and α-ketoglutaramate) and lipids (free fatty acids and docosahexaenoylcarnitine) were consistent with increased proteolysis and lipolysis, indicating a persistent catabolic state in dogs with EPI. Relative abundances of gut microbial metabolites (phenyllactate, 4-hydroxyphenylacetate, phenylacetyl-amino acids, catechol sulfates, and o-cresol-sulfate) were altered in dogs with EPI, consistent with disruptions in gut microbial communities. Increased kynurenine is consistent with the presence of intestinal inflammation in dogs with EPI. Whether these metabolic disturbances participate in the pathophysiology of EPI or contribute to the persistence of clinical signs after treatment is unknown, but they are targets for future investigations.

Original languageEnglish (US)
Article number2313
Issue number14
StatePublished - Jul 2023


  • EPI
  • metabolomics
  • canine
  • dogs
  • pancreas

ASJC Scopus subject areas

  • Animal Science and Zoology
  • General Veterinary


Dive into the research topics of 'Untargeted Analysis of Serum Metabolomes in Dogs with Exocrine Pancreatic Insufficiency'. Together they form a unique fingerprint.

Cite this