Fecal Bile Acids and Microbial Amino Acid Metabolites in Serum are Correlated with Fecal Zonulin in Dogs with Exocrine Pancreatic Insufficiency
ECVIM-CA Online Congress, 2021

P. Barko1; A. Blake2; J. Suchodolski2; J. Lidbury2; J. Steiner2; C. Ameho3; B. Bastien4; D. Williams5

1Pathobiology, University of Illinois, Urbana, IL, USA; 2Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA; 3Nestlé Purina Pet Care, St. Louis, MO, USA; 4Nestlé Purina Research, St. Louis, MO, USA; 5Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA

Dogs with exocrine pancreatic insufficiency (EPI) are treated with pancreatic enzyme replacement therapy (PERT), but up to 40% of dogs have persistent weight loss and diarrhea. EPI is associated with enteric dysbiosis which is known to cause mucosal abnormalities, including increased intestinal permeability, in dogs and other mammals. Mucosal barrier dysfunction could contribute to the persistence of clinical signs in dogs with EPI after PERT. The goal of this study was to detect host-microbiome interactions by correlating serum and fecal concentrations of microbial metabolites with fecal concentrations of zonulin. Zonulin is a biomarker for mucosal barrier integrity and increased fecal zonulin is associated with increased mucosal permeability.

Serum and feces from 20 dogs with EPI and 10 healthy controls were sampled. Dogs with EPI had received PERT for at least 30 days before sampling. To control for the effect of PERT, healthy controls were fed pancreatic enzymes for 14 days before sampling. Serum metabolomes were generated by liquid chromatography-mass spectrometry. Fecal concentrations of unconjugated bile acids were measured by gas chromatography-mass spectrometry. Fecal concentrations of zonulin were measured by ELISA. The Wilcoxon rank-sum test was used to compare fecal metabolites and zonulin between groups. Pearson correlation coefficients were used to detect correlations among serum/fecal metabolites and fecal zonulin.

Fecal zonulin was higher in dogs with EPI compared with healthy controls, but the difference was not statistically significant (p=0.11). Total fecal secondary bile acids were lower in dogs with EPI compared with healthy controls (p=0.03) and inversely correlated with fecal zonulin (r=−0.63, p=0.0006). Total fecal primary bile acids were not significantly different between groups (p=0.430) but were positively correlated with fecal zonulin (r=0.52; p=0.006). Serum taurohyodeoxycholic acid, a secondary bile acid, was inversely correlated with fecal zonulin (r=−0.47, p=0.016). Serum indolepropionate, a microbial tryptophan metabolite, was inversely correlated with fecal zonulin (r=−0.52; p=0.006). Serum N-trimethyl 5-aminovalerate (r=−0.54, p=0.005) and 5-aminovalerate (r=0.47, p=0.015), microbial lysine metabolites, were positively correlated with fecal zonulin. A microbial phenylalanine metabolite, 4-hydroxyphenylacetate, was also positively correlated with fecal zonulin (r=0.39, p=0.047).

Our findings are consistent with previous studies showing altered bile acid metabolism in dogs with EPI. Furthermore, these results indicate a significant effect of microbial bile acid and amino acid metabolism on mucosal barrier function of dogs with EPI. Limitations of this study include the small number of dogs and high false discovery rates for correlations among serum metabolites and fecal zonulin.


This investigation was supported in part by a grant from Nestlé Purina PetCare. Additional funding was provided by Epi4Dogs Inc., a non-profit advocacy organization for EPI research. Five of the authors are affiliated with the Gastrointestinal Laboratory at Texas A&M University (Williams, Suchodolski, Steiner, Lidbury, Blake), which provides commercial diagnostic testing and consultation services. Two of the authors are employees of Nestlé Purina PetCare (Ameho, Bastien) who contributed laboratory support to this investigation unrelated to the partial sponsorship noted above. Two of the authors receive royalties from, and are consultants with, IDEXX Laboratories (Williams, Steiner). Two of the authors serve on the Nestlé Purina PetCare Advisory Board (Williams, Suchodolski). Several of the authors are working on unrelated peer-reviewed research projects funded by veterinary charitable foundations including the Morris Animal Foundation and the American Kennel Club Canine Health Foundation (Barko, Williams, Suchodolski). Two of the authors receive funding for unrelated research (Williams, Barko).


Speaker Information
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P. Barko
University of Illinois
Urbana, IL, USA

MAIN : Poster Presentations : EPI: Bile Acids/Amino Acid Metabolites/Zonulin
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