The essential amino acid tryptophan and its degradation products (e.g., serotonin) are important in the regulation of T-cell response within the intestine as well as intestinal motility. Furthermore, bacteria metabolize tryptophan into various indole-derivatives, which also serve as signaling molecules, activating pathways in other organ systems (e.g., brain, liver, kidney). Alterations in tryptophan metabolism is associated with inflammatory bowel disease (IBD) in humans, and dietary supplementation with tryptophan has been shown to have anti-inflammatory effects in experimental colitis models. The aim of this study was to evaluate changes in the tryptophan-serotonin-indole pathway in dogs with intestinal disease.
Fecal samples from 8 dogs with idiopathic IBD and 10 dogs with acute hemorrhagic diarrhea (AHD) were collected. Fecal samples from 10 healthy dogs were included as a control group. All 28 samples were extracted using methanol-chloroform before targeted analysis by TSQ Altis Triple Quadrupole liquid chromatography-mass spectrometry. Chromatograph peaks were compared with a standard curve for quantification, and adjusted for initial fecal weight. The following metabolites were measured: acetylcholine, anthranilic acid, indole, indole-3-acetaldehyde, indole-3-acetamide, indole-3-acetic acid, indole-3-carboxaldehyde, indole-3-lactic acid, serotonin, tryptamine, tryptophan, and tyramine. Fecal metabolites were compared amongst groups using Kruskal-Wallis tests, followed by Dunn's multiple comparisons tests. Significance was set as p < 0.05.
In the AHD group, anthranilic acid, indole, indole-3-acetamide, and indole-3-lactic acid were significantly increased (p=0.036; 0.004; 0.029; and 0.023, respectively), and serotonin, and tryptamine were decreased (p=0.037; and 0.178, respectively) compared to healthy controls. Fecal tryptophan was increased 2-fold in dogs with IBD (not significant, p=0.524), and 8.5-fold in dogs with AHD (p < 0.001) compared to healthy control dogs.
Significant differences in fecal metabolites from the tryptophan-serotonin-indole pathway were found in dogs with AHD compared to healthy control dogs. Further studies are needed to determine the clinical implications of these differences.
Post Doctoral Research Associate
Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX.
Thursday, June 14
3:00 PM – 3:15 PM
Thursday, June 14
3:15 PM – 3:30 PM
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