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

ABSTRACT

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.

KEYWORDS:

• Epigenetics
• DNA methylation
• plant-based proteins
• intestine
• inflammation
• pea protein concentrate
• soy protein concentrate
• wheat gluten

Acknowledgments

A. S. Bogevik at Nofima (Bergen, Norway) is acknowledged for preparing the zebrafish feed. Tomasz Podgorniak at Norwegian University of Life Sciences (Oslo, Norway) and Ioannis Konstantinidis at the Nord University (Bodø, Norway) are thanked for their recommendations during the bioinformatics analysis.

Authors’ Contributions

AD: Designed the study, conducted the feeding trials and sampling, performed the laboratory work, the bioinformatics analysis and interpretation of the results, and wrote the manuscript.

XC: Contributed significantly to the laboratory work.

DD: Performed the histological analysis.

PS: Contributed significantly to conducting the feeding trials and sampling.

CKF: Conceived and designed the study, provided the reagents, and revised the manuscript.

JF: Conceived and designed the study, provided the reagents, contributed significantly to the bioinformatics analysis and interpretation of the results, and revised the manuscript.

All authors read and approved the manuscript.

Disclosure Statement

The authors reported no potential conflicts of interest.

Ethics Statement

All experiments involving zebrafish were conducted in agreement with the guidelines provided by the Norwegian Animal Research Authority (FOTS ID 12581, 27 July 2017) and approved by the Nord University (Norway) ethics committee.

Supplemental Material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Norwegian Research Council through a post-doctoral fellowship to A.K.S.D. [NFR 267944] and a research grant to C.K.F. [NFR 254822].