METABOLOMICS FROM A DIET INTERVENTION IN ATOPIC DOGS, A MODEL FOR HUMAN RESEARCH?

J. Roine MSc, M. Roine BVMS, A. Hielm-Björkman DVM, PhD

The Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Finland


Introduction

Like humans, dogs too suffer from atopy and allergy. Anecdotal data suggest that a non-heated raw diet may help the disease. Strict diet intervention studies are easy to do on pet dogs as dog owners anyway tend to give their dogs the same food daily for months or years. Targeted metabolomics might shed light on a human/canine common diet related physiology on a biochemical level.

Objectives

To investigate the altered metabolite levels and perturbed metabolic pathways after a dietary intervention in dogs suffering from atopy.

Materials and methods

A randomized controlled diet intervention that comprised either of a commercial high protein, high fat and high mineral raw food (n=13) or a more carbohydrate dense dry food (n=9) was carried out for a median of 5 months. A high-throughput targeted semiquantitative meta-bolomics strategy was applied and 102 metabolites were measured at baseline and at the end of the study. The change from start to end (as %) was calculated for each metabolite as the diet group mean and compared between groups. For significance, Independent samples T-test was used with a p<0.05 (correction not needed for hypothesis generation, but p<0.0005 with Bonferroni).

Results

Among others, the following metabolites were significantly down-regulated in the dry food group while they were up-regulated in the raw food group: Creatine (p=0.007), Cytidine (p<0.0005), Acetylcarnitine (p=0.004), and Decanoylcarnitine (p=0.019). Among others, the following metabolites were up-regulated in the dry food group while they were down-regulated in the raw food group : Glycine (p<0.0005), Dimethyl Glycine (p=0.004), Aminoisobutyric acid (p=0.004), Cytosine (p<0.0005), Proline (p<0.0005), Methionine (p<0.0005), Citrulline  (p<0.0005),  4-Pyridoxic Acid (p=0.005), and Cystathionine (p=0.001).

 


Fig.1: Homocysteine metabolism and metabolites related to it. Metabolites in red boxes were up-regulated and metabolites in blue boxes were  down-regulated in the dry food group.

Discussion

In our study we found that glycine, dimethyl glysine, methionine and cystathione were increased in the blood of dry food group dogs compared to raw food group dogs. All these metabolites are part of the homocysteine metabolism (Fig. 1). Homocysteine concentration of the dogs in the dry food group increased ten times more compared to the dogs in the raw food group, but the difference was not statistically significant (p = 0.08, data not shown). Plasma homocysteine levels have been reported to be elevated in low food folate concentrations (1), in vegan diet compared to omnivores (2), and in vegetarian diet compared to nonvegetarian diet (3) in humans, so the plasma homocysteine might reflect the total protein intake and/or the vitamin B12 and folate status. Increased homocysteine level in blood has been reported to be associated e.g. with chronic kidney disease (4), Alzheimer's disease and vascular disorders (5) in humans.

Cytidine is composed of cytosine and sugar and it can serve as a substrate for the pyrimidine metabolism and it is a protein component.  It is high in organ meats and absorbed intact from the intestine. Acylcarnitines, like acetylcarnitine and decanoylcarnitine, are produced from fatty acids and carnitine. The raw food had higher fat and meat content than the dry food. Red meat is rich in carnitine and creatine. The high serum concentration of these metabolites in the raw food group might be due to the raw diet's high meat and fat content. 

Conclusions

It is unclear if the different diet composition or the way of processing the foods, i.e. if it was non-heated or heated, had an impact on the results. However, we propose that the dog should be further studied as a model for human research.

References:

  1. Ashfield-Watt PA, Pullin CH, et al. Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial. Am J Clin Nutr. 2002;76:180-6.
  2. Majchrzak D, Singer I, et al. B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans. Ann Nutr Metab. 2006;50:485-91.
  3. Huang YC, Chang SJ, et al. The status of plasma homocysteine and related B-vitamins in healthy young vegetarians and nonvegetarians. Eur J Nutr. 2003;42:84-90.
  4. Chao MC, Hu SL, et al. Serum homocysteine level is positively associated with chronic kidney disease in a Taiwan Chinese population. J Neophrol. 2014:27:299-305.
  5. Madsen SK, Rajagopalan P, et al. Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative.  Neurobiol Aging. 2015;36 Suppl 1:S203-10.

 

 We want to thank our sponsors:

•Svenska kulturfonden and MILA Laboratories

•However, none of the sponsors have had any influence on the reporting of data.

FENS 2015: European Nutrition Conference. October 2015. Berlin, Germany.