Obesity, Nutrition and the Multiple Sclerosis Risk in Adolescents

Highlights: What are the main findings? Multiple Sclerosis (MS) involves a distinct prodromal phase. Obesity is an independent risk factor, inducing metabolic stress and epigenetic reprogramming that establish a pro-inflammatory environment that lowers the threshold for autoimmune activation. The pathogenesis of MS involves a dysfunctional gut–liver–brain axis where diet-induced dysbiosis and secondary bile acid modification trigger systemic inflammation, leading to blood–brain barrier disruption and sustained neuroinflammation. What are the implications of the main findings? The Mediterranean Diet serves as a biologically active determinant of immune regulation rather than a mere lifestyle factor, with higher adherence significantly associated with reduced MS risk and improved clinical outcomes. Metabolic interventions, including GLP-1 receptor agonists and bile acid modulation, represent promising therapeutic strategies that can provide dual benefits by managing obesity while exerting direct neuroprotective effects. Multiple Sclerosis (MS) is a chronic, autoimmune neurological disease resulting from the interplay between genetic susceptibility and environmental factors. In recent decades, the rising incidence of MS, particularly pediatric-onset forms, has paralleled the global obesity pandemic. This article explores the causal link between pediatric obesity, systemic inflammation, and neuroinflammation, with a specific focus on the microbiota–gut–liver–brain axis. We analyze how nutritional habits can play a pivotal role by inducing dysbiosis, with alteration in microbiota-driven metabolites, and leaky gut related abnormalities—which may trigger blood–brain barrier (BBB) disruption and microglial activation—or by acting as a protective factor, such as through the Mediterranean Diet (MD). Furthermore, we evaluate the emerging therapeutic perspectives offered by Glucagon-Like Peptide-1 (GLP-1) agonists, which may offer dual benefits in weight management and immune modulation.