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 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.
Highlights
Canine inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal (GI) diseases in dogs [1, 2]
The principal component analysis (PCA) (Figure 2A) and partial least squares-discriminant analysis (PLS-DA) (Figure 2B) plots revealed a clustering for pre-treatment vs. post-treatment 1 (GAG+PRB) and post-treatment 2, indicating that both of the treatments had a significant impact on the canine serum metabolome
Despite the fact that the samples in the post-treatment 2 group are more distributed along principal component 2 in both PCA and PLS-DA, there was no clear separation between treatment 1 and treatment 2
Summary
Canine inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal (GI) diseases in dogs [1, 2]. It is caused by an interplay of genetic susceptibility, intestinal dysbiosis, diet, and other environmental factors, similar to human IBD [3, 4]. Several hydrolyzed diets have been developed for the treatment of Crohn’s disease in humans [4, 5] and dogs [3] These diets are considered hypoallergenic because the hydrolysis process disrupts protein structures to limit existing allergens and allergenic epitopes, thereby making the diets unlikely to stimulate the immune system [6, 7]. Hydrolyzed diets are clinically highly effective for the long-term treatment of both FRE and IBD [8]. It is not known how such diets impact metabolic processes that coincide with these beneficial effects, which requires the study of serum metabolite profiles
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