高强度甜味剂多系统效应的斑马鱼证据

Multisystem Effects of High-Intensity Sweeteners: Evidence from Zebrafish

摘要: 高强度甜味剂因甜度高、添加量低，广泛用于减糖食品。近年来，除传统毒理学终点外，其对肠道屏障、微生物群、糖脂代谢及神经行为的潜在影响受到关注。斑马鱼具有发育快、幼体透明、易于高通量成像和多系统终点整合等特点，已用于糖精、阿斯巴甜、安赛蜜、三氯蔗糖和纽甜等甜味剂的生物效应研究。现有证据显示，不同甜味剂具有明显的分子特异性：安赛蜜和纽甜在特定暴露条件下可引起肠道屏障与炎症改变，部分甜味剂还伴随菌群功能、糖脂代谢、氧化应激及神经行为变化。本文以斑马鱼研究为主线，结合哺乳动物和微生物证据，梳理肠道稳态、菌群代谢、肠–肝轴和肠–脑轴的可能联系。总体上，斑马鱼适合用于高强度甜味剂的多终点筛查与机制筛选，但其结果不能直接外推为人体健康风险，仍需结合实际膳食暴露、毒代动力学及因果干预研究综合判断。

Abstract: High-intensity sweeteners are widely used in sugar-reduced foods because they provide intense sweetness at low addition levels. Beyond conventional toxicological endpoints, increasing attention has focused on their potential effects on intestinal barrier function, gut microbiota, glucose and lipid metabolism, oxidative stress, and neurobehavior. Zebrafish, with rapid development, transparent larvae, high-throughput imaging, and integrated multisystem endpoints, have been used to evaluate saccharin, aspartame, acesulfame potassium, sucralose, neotame, and related sweeteners. Available evidence indicates compound-specific effects: under defined exposure conditions, acesulfame potassium and neotame can alter intestinal barrier and inflammatory phenotypes, while several sweeteners are associated with changes in microbial function, metabolic homeostasis, and neurobehavior. This review summarizes zebrafish evidence on intestinal homeostasis, microbial metabolism, and potential gut-liver and gut-brain interactions, supplemented by selected mammalian and microbial studies. Zebrafish are useful for multi-endpoint and mechanistic screening, but their findings should not be directly interpreted as evidence of human health risk without considering dietary exposure, toxicokinetics, and causal intervention studies.