Dietary inclusion of plant ingredients induces epigenetic changes in the intestine of zebrafish

Epigenetic modifications, such as DNA methylation, can be regulated by nutrition and dietary factors. There has been a large increase in the use of sustainable plant-based protein sources in fish feed due to limitations of fishmeal resources, which are needed to sustain a rapidly growing aquaculture industry. With this major transition from marine ingredients to plant-based diets, fish are abruptly introduced to changes in dietary composition and exposed to a variety of phytochemicals, some of which known to cause epigenetic changes in mammals. However, the effect of plant ingredients on the epigenome of fish is barely understood. In the present study, the nutriepigenomic effects of the addition of pea, soy, and wheat gluten protein concentrate to aquafeeds were investigated using zebrafish as a model. A genome-wide analysis of DNA methylation patterns was performed by reduced representation bisulphite sequencing to examine global epigenetic alterations in the mid intestine after a 42-day feeding trial. We found that inclusion of 30% of wheat gluten, pea and soy protein concentrate in the diet induced epigenetic changes in the mid intestine of zebrafish. A large number of genes and intergenic regions were differentially methylated with plant-based diets. The genes concerned were related to immunity, NF‐κB system, ubiquitin-proteasome pathway, MAPK pathway, and the antioxidant defence system. Epigenetic regulation of several biological processes, including neurogenesis, cell adhesion, response to stress and immunity was also observed. Ultimately, the observed epigenetic changes may enable zebrafish to rapidly regulate inflammation and maintain intestinal homoeostasis when fed plant protein–based diets.

营养与膳食因素可调控表观遗传修饰（epigenetic modifications），例如DNA甲基化（DNA methylation）。鉴于鱼粉资源有限，而快速发展的水产养殖业对鱼粉需求旺盛，水产饲料中可持续性植物基蛋白源的应用已大幅增长。随着从海洋原料向植物基饲料的转型，鱼类会突然面临日粮组成的变化，并接触到多种植物化学物——其中部分物质已被证实可在哺乳动物中诱发表观遗传改变。然而，植物原料对鱼类表观组的影响却鲜为人知。本研究以斑马鱼（zebrafish）为模型，探究了在水产饲料中添加豌豆、大豆及小麦谷蛋白浓缩物所产生的营养表观基因组学（nutriepigenomic）效应。本研究通过简化代表性亚硫酸氢盐测序（reduced representation bisulphite sequencing）技术，对42天饲喂试验后斑马鱼中肠的全基因组DNA甲基化模式进行了分析，以探究其整体表观遗传改变。结果发现，日粮中添加30%的小麦谷蛋白、豌豆及大豆蛋白浓缩物，可诱导斑马鱼中肠发生表观遗传改变。植物基饲料组中，大量基因及基因间区（intergenic regions）呈现差异甲基化状态。相关基因涉及免疫、核因子κB（NF‐κB）系统、泛素-蛋白酶体通路（ubiquitin-proteasome pathway）、丝裂原活化蛋白激酶（MAPK）通路以及抗氧化防御系统。研究还观察到，神经发生、细胞黏附、应激响应及免疫等多种生物学过程均存在表观遗传调控现象。最终，此类表观遗传改变可帮助斑马鱼在摄入植物基饲料时，快速调控炎症反应并维持肠道稳态。