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. 2021 Aug 5;11(1):15881.
doi: 10.1038/s41598-021-94464-2.

Investigation of diets associated with dilated cardiomyopathy in dogs using foodomics analysis

Caren E Smith  1 , Laurence D Parnell  2 , Chao-Qiang Lai  2 , John E Rush  3 , Lisa M Freeman  4
Affiliations

Investigation of diets associated with dilated cardiomyopathy in dogs using foodomics analysis

Caren E Smith et al. Sci Rep. .

Abstract

Dilated cardiomyopathy (DCM) is a disease of the heart muscle that affects both humans and dogs. Certain canine diets have been associated with DCM, but the diet-disease link is unexplained, and novel methods are needed to elucidate mechanisms. We conducted metabolomic profiling of 9 diets associated with canine DCM, containing ≥ 3 pulses, potatoes, or sweet potatoes as main ingredients, and in the top 16 dog diet brands most frequently associated with canine DCM cases reported to the FDA (3P/FDA diets), and 9 non-3P/FDA diets. We identified 88 named biochemical compounds that were higher in 3P/FDA diets and 23 named compounds that were lower in 3P/FDA diets. Amino acids, amino acid-derived compounds, and xenobiotics/plant compounds were the largest categories of biochemicals that were higher in 3P/FDA diets. Random forest analyses identified the top 30 compounds that distinguished the two diet groups with 100% predictive accuracy. Four diet ingredients distinguished the two diet groups (peas, lentils, chicken/turkey, and rice). Of these ingredients, peas showed the greatest association with higher concentrations of compounds in 3P/FDA diets. Moreover, the current foodomics analyses highlight relationships between diet and DCM in dogs that can identify possible etiologies for understanding diet-disease relationships in dogs and humans.

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Conflict of interest statement

In the last 3 years, Dr. Freeman has received research funding from, given sponsored lectures for, and/or provided professional services to Aratana Therapeutics, Elanco, Hill’s Pet Nutrition, Nestlé Purina PetCare, P&G Pet Care (now Mars), and Royal Canin. In the last 3 years, Dr. Rush has received research funding from, given sponsored lectures for, and/or provided professional services to Aratana Therapeutics, Boehringer Ingelheim, Elanco, IDEXX, Nestlé Purina PetCare, and Royal Canin. None of the other authors has any competing interests to declare.

Figures

Figure 1
Figure 1
Illustration of 830 biochemical compounds that were significantly different between diet groups. Diets were assigned to one of two groups: (1) associated with clinical cases of dilated cardiomyopathy (DCM) in dogs; containing ≥ 3 pulses, potatoes, or sweet potatoes in the top 20 ingredients; and in the top 16 dog food brands named most frequently in DCM cases reported to the FDA (3P/FDA) or (2) not meeting the above criteria (non-3P/FDA). The beta values, where a negative value denotes higher levels in the 3P/FDA diet group, are plotted against the negative of log10(P value). Compounds plotted in gray have P values above the cutoff of 5.80E−05, and are considered as not statistically significantly different between diet groups. Triangles indicate compounds that distinguish the two diet groups based on random forest analysis. Those compounds featured in this manuscript are labeled.
Figure 2
Figure 2
Relationships between four key ingredients and biochemical compounds found to distinguish 3P/FDA from non-3P/FDA diet groups. Panels illustrate the data as follows: (a) pea; (b) lentil; (c) chicken/turkey; (d) rice. For each of four ingredients that distinguished 3P/FDA and non-3P/FDA diets (i.e., peas, lentils, chicken/turkey, and rice), the mean level of each compound was compared between diets high versus absent in each ingredient (e.g., diets high in peas compared to diets containing no peas). The P value is depicted as − 1*(log10[P value]) on the x-axis. Solid (filled) bars indicate a significant positive correlation between compound and ingredient (e.g., diets high in peas had significantly higher levels of a compound compared to diets with no peas), while open bars indicate a significant negative correlation between compound and ingredient. For relationships that do not meet statistical significance, no bar is plotted. Colors represent the classification of the compounds: red, amino acids; orange, xenobiotics and plant-derived compounds; light green, lipid; dark green, carbohydrate; cyan, cofactors and vitamins; blue, energy; violet, nucleotides; yellow, peptide; gray, partially characterized; black, unnamed. The designation RF30 indicates a member of 30 compound set determined by random forest analyses to distinguish the 3P/FDA and non-3P/FDA diet groups.
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