Treatment With Hydrolyzed Diet Supplemented With Prebiotics and Glycosaminoglycans Alters Lipid Metabolism in Canine Inflammatory Bowel Disease

Abstract

Canine inflammatory bowel disease (IBD) is a chronic, immunologically mediated intestinal disorder, resulting from the complex interaction of genetic, environmental and immune factors. Hydrolyzed diets are used in dogs with food-responsive diarrhea (FRD) to reduce adverse responses to immunostimulatory proteins. Prebiotics (PRBs) and glycosaminoglycans (GAGs) have previously been demonstrated to show anti-inflammatory activity in the intestinal mucosa. Notably, hydrolyzed diets combined with the administration of PRBs and GAGs offer a promising approach for the treatment of canine IBD. Our aim was to investigate the effects of hydrolyzed diet and GAG+PRB co-treatment on the serum metabolomic profile of IBD dogs. Dogs with IBD randomly received either hydrolyzed diet supplemented with GAGs and PRBs (treatment 1) or hydrolyzed diet alone (treatment 2) for 10 weeks. A targeted metabolomics approach using mass spectrometry was performed to quantify changes in the serum metabolome before and after treatment and between treatment 1 and 2. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), hierarchical cluster analysis (HCA) and univariate statistics were used to identify differences between the treatment groups. PCA, PLS-DA, and HCA showed a clear clustering of IBD dogs before and after hydrolyzed diet, indicating that the treatment impacted the serum metabolome. Univariate analysis revealed that most of the altered metabolites were involved in lipid metabolism. The most impacted lipid classes were components of cell membranes, including glycerophospholipids, sphingolipids, and di-and triglycerides. In addition, changes in serum metabolites after GAG+PRB co-treatment suggested a possible additional beneficial effect on the lipid metabolism in IBD dogs. In conclusion, the present Ambrosini et al. Lipid Metabolism in Canine IBD study showed a significant increase in metabolites that protect gut cell membrane integrity in response to hydrolyzed diet alone or in combination with GAG+PRB co-treatment. Administration of such treatment over 70 days improved selected serum biomarkers of canine IBD, possibly indicating improved intestinal membrane integrity.

A Preliminary Metabolomic Study of Yorkshire Terrier Enteropathy

“…However, in another study, treatment with a novel protein diet and treatment with prednisolone for 4 weeks had a significant impact on the phospholipid profile in dogs with chronic enteropathies [ 30 ]. Additionally, a recently published study revealed an altered lipid metabolism after 10 weeks of feeding a hydrolyzed diet to dogs with chronic enteropathies [ 60 ]. Therefore, the timeframe of 70 days chosen in our study should have been sufficient to reveal a recovery of altered metabolites.…”

Harnessing the Biology of Canine Intestinal Organoids to Heighten Understanding of Inflammatory Bowel Disease Pathogenesis and Accelerate Drug Discovery: A One Health Approach

“…Furthermore, expression of pro-inflammatory cytokines and antimicrobial peptides produced by Paneth cells were also identified. In addition to structural and compositional relevance, functionality was also demonstrated by these authors (Mochel et al, 2017;Chandra et al, 2019;Ambrosini et al, 2020a). In this same study, canine organoids demonstrated metabolic activity during differentiation, functional cystic fibrosis transmembrane conductive regulator (CFTR) chloride channels and uptake of exosome-like vesicles secreted by the parasite Ascaris suum (Chandra et al, 2019).…”

“…Such abnormalities include a large number of IgE positive cells in dogs with cIBD ( Locher et al, 2001 ), a decrease in mast cell numbers with a concomitant increase in CD3+ cells, IgG+ plasma cells, CD11c cells and reduced Treg cells ( Jergens et al, 1996 ; Jergens et al, 1998 ; German et al, 2001 ; Kathrani et al, 2011b ; Schmitz et al, 2012 ). Furthermore, diet has also been shown to impact mucosal microbiota and the GI metabolome and mucosal microbiota in dogs with cIBD ( Atherly et al, 2019 ; Ambrosini et al, 2020a ). Recently, early-life risk factors for developing IBD have been an area of interest and studies have identified similar findings in dogs and humans with cIBD/IBD such as an association with early life high-fat low-carbohydrate diets and the later development of IBD/cIBD ( Hemida et al, 2021 ).…”

The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy

“…In the veterinary field, this subject has also been recently reported, with significant variances identified in plasmatic and whole blood phospholipid profiles of dogs with IRE and FRE [ 23 ], and in dogs with IBD after a hydrolyzed diet [ 24 ]; however, no information is available on the erythrocyte membrane lipidome. To choose the representative cell type, it must be considered that red blood cells are the largest contributors to cell numbers in the body and make up the highest number of cells formed every day [ 25 ].…”