神经系统疾病饮食干预：从“脑先/体先”到代谢-表观-免疫-肠-脑轴整合模型

Dietary interventions in neurological disorders: an integrative framework of the brain-first/body-first etiology, systemic metabolism-epigenome-immunity network and gut-brain axis

摘要

神经系统疾病是全球性的重大健康问题，传统药物治疗往往存在诸多局限性，例如药物的毒副反应。饮食干预作为一种非侵入性、可及性强的策略，近年来在神经科学领域获得广泛关注。本文系统阐述了饮食干预在神经系统疾病管理中的双重作用机制：一方面通过调节中枢内的代谢-表观-免疫网络直接影响脑功能；另一方面通过重塑肠-脑轴，从外周调控脑健康。本文首次将“脑先”与“体先”发病模型与代谢-表观-免疫网络、肠-脑轴进行理论整合，构建了一个跨中枢-外周的饮食干预系统框架。基于该框架，本文梳理了代表性饮食成分（如多酚、ω-3脂肪酸、益生元）与饮食模式（如地中海饮食、生酮饮食、间歇性断食）的作用路径与疗效，指出当前研究在机制研究、方案标准化与个体化应用方面的不足，并展望了未来通过多组学技术、精准营养与跨学科合作推动饮食干预临床转化的方向。本文提出的整合模型不仅为理解饮食在神经系统疾病中的多靶点作用提供了统一的理论视角，也为未来个体化营养干预策略的设计与临床转化提供了重要的学术依据与实践指导。

Abstract

Neurological disorders represent a major and growing global health burden, for which conventional pharmacotherapies often have limited efficacy and notable side effects. Dietary intervention has thus gained prominence as a viable, non-invasive, and accessible adjunctive strategy. This review proposed a novel integrative framework to decipher the multisystem mechanisms of diet. We posited that dietary influences converge through two interconnected pathways: a direct central modulation of the intracerebral metabolism-epigenome-immunity network, and a peripheral-to-central signaling route via the gut-brain axis. This article tried to come up with a first synthesis of the “brain-first” and “body-first” etiological models with the systemic metabolism-epigenome-immunity network and gut-brain axis mechanisms, constructing a unified paradigm that bridges central and peripheral pathophysiology. Grounded in this framework, we critically evaluated the roles of specific dietary components (e. g., polyphenols, ω-3 fatty acids, pre/probiotics) and holistic dietary patterns (e. g., Mediterranean diet, ketogenic diet, intermittent fasting), elucidating their distinct yet complementary sites of action within the proposed network. We further identified persistent challenges in mechanistic delineation, protocol standardization and personalization of interventions. Looking forward, we highlighted the transformative potential of multi-omics technologies, precision nutrition, and interdisciplinary convergence in translating this integrated model into tailored, evidence-based dietary strategies. This theoretical synthesis not only offers a cohesive lens via which to understand the pleiotropic actions of diet in neurology but also provides a foundational road-map for advancing personalized nutritional neuroscience from bench to bedside.

关键词

神经系统疾病 / 饮食干预 / 肠-脑轴 / 代谢-表观-免疫网络 / 脑先/体先理论 / 营养神经科学

Key words

neurological disorders / dietary intervention / gut-brain axis / metabolism-epigenome-immunity network / brain-first/body-first theory / nutritional neuroscience

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基金资助

国家生物育种科技重大专项(2023ZD04046)

国家自然科学基金重点项目(32130099)

中国博士后科学基金会与湖南省联合资助(2025T021HN)