Beyond Neuroinflammation: Targeting the Microbe-Barrier-Brain Axis Through Precision Nutrition in Neurological Long...

Post-acute Neurological Sequelae of SARS-CoV-2 infection (Neuro-PASC) contribute substantially to Long COVID-related disability, with cognitive impairment, chronic fatigue, dysautonomia, and neuropsychiatric symptoms among its most debilitating manifestations. Although its pathogenesis remains incompletely understood, evidence implicates persistent immune activation, intestinal barrier dysfunction, microbiota dysbiosis, microbiome-derived metabolic alterations, mitochondrial dysfunction, and neuroimmune interactions in sustaining neuroinflammation and neurological impairment. This narrative review examines precision nutrition as a potential pathway-oriented strategy for Neuro-PASC. We synthesise evidence linking the gut microbiota, intestinal permeability, immunometabolic pathways, mitochondrial function, and neurological outcomes, while evaluating nutritional interventions targeting these mechanisms. We focus on candidate biomarkers, including serum zonulin, fatty acid-binding protein 2 (FABP2), faecal short-chain fatty acids (SCFAs), and the kynurenine-to-tryptophan ratio, which may support patient stratification and personalised nutritional strategies. We also propose a stepwise framework involving dietary stabilisation, functional foods, targeted supplementation, and microbiome-based interventions, alongside practical considerations for post-exertional symptom exacerbation, dysautonomia, and mast cell-related symptoms. Finally, we identify priorities for future research, including multi-omics integration, artificial intelligence, digital health, and biomarker-stratified randomised controlled trials. Because current evidence remains predominantly observational and mechanistic, precision nutrition should be considered a complementary strategy requiring rigorous clinical validation.