Beyond Neuroinflammation: Targeting the Microbe–Barrier–Brain Axis Through Precision Nutrition in Neurological Long COVID (Neuro-PASC)
- 1Hospital Central de La Defensa “Gómez Ulla”, 28047 Madrid, Spain
- 2Department of Nursing, Physiotherapy and Medicine, University of Almería, 04120 Almería, Spain
- 3Food Technology Division, University of Almería, 04120 Almería, Spain
Abstract
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.
Related
- The cGAS-STING Pathway in Neuroinflammation and Neurological Disease: Mechanisms, Disease Contexts, and Periphery-to-Brain Communication
- Continuous Glucose Monitoring for Metabolic Phenotyping and Precision Nutrition: Current Evidence, Clinical Applications and Future Perspectives
- Targeting the cGAS-STING axis in Alzheimer’s disease: neuroinflammation-centric therapeutic strategies and perspectives
- Targeting Ninjurin-1-Mediated Microglial Pyroptosis Attenuates Neuroinflammation and Neuronal Injury Following Intracerebral Hemorrhage.
- Noncoding RNA control of neuroinflammation in Alzheimer’s disease: from immune cell states to precision therapeutics
BibTeX
@article{castrobono2026beyond,
title = {{Beyond Neuroinflammation: Targeting the Microbe–Barrier–Brain Axis Through Precision Nutrition in Neurological Long COVID (Neuro-PASC)}},
author = {Amador Velázquez De Castro-Bono and Gracia Castro-Luna and José Luis Guil-Guerrero},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18203420},
url = {https://www.mdpi.com/2072-6643/18/20/3420},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond Neuroinflammation: Targeting the Microbe–Barrier–Brain Axis Through Precision Nutrition in Neurological Long COVID (Neuro-PASC)
AU - Amador Velázquez De Castro-Bono
AU - Gracia Castro-Luna
AU - José Luis Guil-Guerrero
PY - 2026
DA - 2026/10/01
JO - Nutrients
DO - 10.3390/nu18203420
UR - https://www.mdpi.com/2072-6643/18/20/3420
AB - 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.
SN - 2072-6643
ER -