Canine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A Scoping Review Highlighting Metabolic Perspectives Beyond the Brain

Background: Emerging evidence indicates that epilepsy extends beyond the brain, involving systemic metabolic, immune, and microbiome perturbations that shape neuronal excitability and treatment response. Canine idiopathic epilepsy (CE) offers a naturally occurring model with strong electrophysiological, pharmacological, and clinical homology to human epilepsies. Methods: This scoping review was conducted according to the PRISMA-ScR guidelines. A systematic literature search was performed in Web of Science and MEDLINE (PubMed) to identify original studies reporting metabolic, immunometabolic, or neurochemical alterations in CE compared with healthy controls. Eligible studies included peer-reviewed original research involving client-owned dogs diagnosed with CE according to international consensus criteria (IVETF guidelines). Studies focusing exclusively on genetics or neuroimaging without metabolic outcomes were excluded. Titles, abstracts, and full texts were screened for eligibility, and data were extracted from included studies using a standardized approach. Identified metabolic domains were synthesized narratively and grouped into functional systems, including amino acid and lipid metabolism, micronutrients, neurotransmission, oxidative stress, inflammation and immunology, endocannabinoid signalling, microRNAs, and gut–brain axis-related pathways. In a second step, the identified metabolic domains were evaluated for translational relevance through a targeted, non-systematic narrative synthesis of the human epilepsy literature. This approach aimed to assess cross-species parallels and to provide a conceptual framework to guide future research, rather than to perform a comprehensive systematic review of metabolic alterations in human epilepsy. Results: Across CE studies, consistent alterations were observed in multiple interconnected functional systems, including metabolic, immune, and gut–brain axis pathways, in agreement with findings reported for human epilepsy. These data support a model of epileptogenesis involving systemic dysfunction beyond the central nervous system. Translationally, these findings suggest opportunities for biomarker development, patient stratification, and mechanism-based interventions, including dietary and metabolic approaches (e.g., medium-chain triglyceride supplementation), microbiome modulation, and immunometabolic targeting. The current evidence is limited by small and heterogeneous cohorts, potential confounding effects of antiseizure medications, variability in dietary and fasting conditions, breed-related effects, and a predominance of associative over causal relationships. Conclusions: This review positions CE as a reference framework for future research into epilepsy metabolism, integrating current evidence and its translational relevance to human disease. The findings support a shift toward a systems-level view of epileptogenesis, involving interconnected metabolic, immune, and gut–brain axis pathways beyond the brain. CE represents a valuable translational model to identify shared mechanisms, inform biomarker discovery, and guide the development of mechanism-based therapeutic strategies across veterinary and human epilepsy.