Research Article: Comparison of the systemic phospholipid profile in dogs diagnosed with idiopathic inflammatory bowel disease or food-responsive diarrhea before and after treatment

Date Published: April 16, 2019

Publisher: Public Library of Science

Author(s): Katja Kalenyak, Romy M. Heilmann, Chris H. A. van de Lest, Jos F. Brouwers, Iwan A. Burgener, Mathias Chamaillard.


Inflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are common chronic enteropathies in dogs, of which the exact pathogenesis has not been fully understood. In people dyslipidemia has been reported in patients with IBD, and potential therapeutic benefits of polyunsaturated fatty acids (PUFA) in the treatment of IBD have been investigated. Studies on the phospholipid profile in dogs with IBD and FRD are still lacking.

To investigate the systemic phospholipid profile of dogs with IBD or FRD and to evaluate possible differences in phospholipids before and after treatment.

The phospholipids in whole blood and EDTA plasma of 32 dogs diagnosed with either IBD (n = 16) or FRD (n = 16) were analyzed by hydrophilic interaction liquid chromatography (HILIC) prior to and after initiation of treatment, which included an elimination diet enriched with PUFAs.

A clear separation of the phospholipids between whole blood and plasma was demonstrated on principal component analysis plots. In addition to the type of specimen, treatment and disease severity were the most significant factors determining the variance of the phospholipid profile. An increase in lysolipids was observed after treatment. The phosphatidylcholine (PC) species changed from PC 38:4 before treatment to mainly lysophosphatidylcholine 18:0 after treatment. Furthermore, several differences in the abundance of individual phospholipids were identified between dogs with IBD and dogs with FRD and between treatment statuses using random forest analysis.

Significant variances were identified in the phospholipid profiles of dogs with IBD and FRD. These were particularly determined by type of specimen used, disease severity and treatment status. After treatment, a shift of phospholipid species towards lysophosphatidylcholine 18:0 was observed. Future studies should further investigate the role of lipids in the pathophysiology of IBD and FRD as well as their potential therapeutic benefits.

Partial Text

Chronic inflammatory enteropathies (CIE) are a group of common disorders in dogs, which are categorized based on the patient’s response to treatment as either food-responsive diarrhea (FRD), antibiotic-responsive diarrhea (ARD), or idiopathic inflammatory bowel disease (IBD) [1–4]. Dogs with FRD will show a complete clinical response after dietary modification to a novel source of protein and carbohydrates or to a commercially available hydrolyzed protein diet [5,6], whereas dogs with ARD require the use of antibiotic treatment, for example with tylosin, in addition to dietary management for clinical signs of gastrointestinal disease to resolve [7–9]. Idiopathic IBD is defined as chronic gastrointestinal signs of a complex pathogenesis, histologic confirmation of intestinal inflammation, and the necessity for anti-inflammatory and / or immunosuppressive treatment [2,4,7,10]. To date, the etiopathogenesis of CIE, in particular of idiopathic IBD, has not been fully unraveled. However, the current state of knowledge strengthens the notion that a combination of a genetic susceptibility [11–15], dietary and environmental factors, the intestinal microbiota, and an exaggerated immune response contribute to the development of idiopathic IBD in dogs [16–20]. This complexity involving the pathogenesis of IBD urgently asks for potential novel treatment strategies in addition to the currently used stepwise treatment approach of dietary modification, antibiotic trials, and immunosuppressive treatment [2,3]. Novel approaches, including beneficial alterations in the intestinal microbiota through the administration of probiotics and / or prebiotics [21–26] or fecal microbial transplants [27–29], have recently attracted great attention and warrant further research to fully elucidate their therapeutic potential or benefit.

This is the first study to investigate the systemic phospholipid profile in samples from dogs diagnosed with IBD or FRD and to evaluate changes in the phospholipid profile following the initiation of treatment in these dogs. Significant differences were observed in the phospholipid profiles in dogs with CIE, especially between the two different types of specimen used (whole blood vs. plasma), disease category (IBD vs. FRD), and treatment status. An explanation for the distinct phospholipid profiles in whole blood and plasma samples as discovered by PCA could be the difference in the number of cells within these sample types. As lipids, including phospholipids, are essential components of cellular membranes [70,71], it appears reasonable to expect a difference in the phospholipid composition between whole blood (which contains erythrocytes, leukocytes, and platelets) and plasma (which is essentially devoid of these cells but contains lipoproteins). An influence of different packed cell volumes or numbers of leukocytes of the patients on the findings of this study can currently not be fully excluded. In the current study, slightly more significant effects were found in plasma samples than in whole blood samples. This finding, in addition to a generally better storage stability of plasma [72] as well as less disturbance of the interpretation due to a lower number of unrelated lipids present in the cell membranes, leaves–in the authors’ opinion–plasma the preferable sample type for future studies on the phospholipid profile.