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Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy.

ABSTRACT: Consumption of diets containing medium-chain TAG (MCT) has been shown to confer neuroprotective effects. We aim to identify the global metabolic perturbations associated with consumption of a ketogenic diet (medium-chain TAG diet (MCTD)) in dogs with idiopathic epilepsy. We used ultra-performance liquid chromatography-MS (UPLC-MS) to generate metabolic and lipidomic profiles of fasted canine serum and made comparisons between the MCTD and standardised placebo diet phases. We identified metabolites that differed significantly between diet phases using metabolite fragmentation profiles generated by tandem MS (UPLC-MS/MS). Consumption of the MCTD resulted in significant differences in serum metabolic profiles when compared with the placebo diet, where sixteen altered lipid metabolites were identified. Consumption of the MCTD resulted in reduced abundances of palmitoylcarnitine, octadecenoylcarnitine, stearoylcarnitine and significant changes, both reduced and increased abundances, of phosphatidylcholine (PC) metabolites. There was a significant increase in abundance of the saturated C17 : 0 fatty acyl moieties during the MCTD phase. Lysophosphatidylcholine (17 : 0) (P=0·01) and PC (17:0/20:4) (P=0·03) were both significantly higher in abundance during the MCTD. The data presented in this study highlight global changes in lipid metabolism, and, of particular interest, in the C17 : 0 moieties, as a result of MCT consumption. Elucidating the global metabolic response of MCT consumption will not only improve the administration of current ketogenic diets for neurological disease models but also provides new avenues for research to develop better diet therapies with improved neuroprotective efficacies. Future studies should clarify the involvement and importance of C17 : 0 moieties in endogenous MCT metabolic pathways.

SUBMITTER: Law TH

PROVIDER: S-EPMC6137430 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy.

Law Tsz Hong TH Volk Holger A HA Pan Yuanlong Y Zanghi Brian B Want Elizabeth J EJ

The British journal of nutrition 20180713 5

Consumption of diets containing medium-chain TAG (MCT) has been shown to confer neuroprotective effects. We aim to identify the global metabolic perturbations associated with consumption of a ketogenic diet (medium-chain TAG diet (MCTD)) in dogs with idiopathic epilepsy. We used ultra-performance liquid chromatography-MS (UPLC-MS) to generate metabolic and lipidomic profiles of fasted canine serum and made comparisons between the MCTD and standardised placebo diet phases. We identified metabolit ...[more]

PMID: 30001753

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Project description:Consumption of diets containing medium chain triglycerides have been shown to confer neuroprotective and behavior modulating effects. We aimed to identify metabolic and microbiome perturbations in feces that are associated with consumption of a medium chain triglyceride ketogenic diet (MCT-KD) in dogs with idiopathic epilepsy. We used 16S rRNA gene sequencing to generate microbiome profiles and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to generate lipidomic profiles of canine feces. We made comparisons between the MCT-KD, standardized placebo diet and baseline pre-trial diet phases. Consumption of the MCT-KD resulted in a significant increase in the species richness (?-diversity) of bacterial communities found in the feces when compared to the baseline diet. However, phylogenetical diversity between samples (beta-diversity) was not affected by diet. An unnamed Bacteroidaceae species within genus 5-7N15 was identified by LEfSe as a potential biomarker associated with consumption of the MCT-KD, showing an increased abundance (p = 0.005, q = 0.230) during consumption of MCT-KD. In addition, unclassified members of families Erysipelotrichaceae (p = 0.013, q = 0.335) and Fusobacteriaceae (p = 0.022, q = 0.358) were significantly increased during MCT-KD consumption compared to baseline. Blautia sp. and Megamonas sp. instead were decreased during consumption of either placebo or MCT-KD (p = 0.045, q = 0.449, and p = 0.039, q = 0.449, respectively). Bacteroidaceae, including genus 5-7N15, have previously been associated with non-aggressive behavior in dogs. In addition, 5-7N15 is correlated in humans with Akkermansia, a genus known to be involved in the neuroprotective effect of ketogenic diets in mice models of seizures. Five metabolite features, tentatively identified as long chain triglycerides, were significantly higher after consumption of the placebo diet, but no unique features were identified after consumption of the MCT-KD. The data presented in this study highlight significant changes shown in both the fecal microbiome and lipidome as a result of consumption of the MCT-KD. Elucidating the global canine gut response to MCT consumption will improve our understanding of the potential mechanisms which confer anti-seizure and behavior modulating effects. Further studies should aim to characterize the gut microbiome of both dogs with epilepsy and healthy controls.

Dataset Information

Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy.

Publications

Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy.

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