Fish Sidestream-Derived Protein Hydrolysates Suppress DSS-Induced Colitis by Modulating Intestinal Inflammation in Mice.

Maria G Daskalaki,Tone Aspevik,Ioanna Lapi,Konstantinos Axarlis,Ourania Kolliniati,Christos Tsatsanis,Katerina Kousoulaki,Maria Venihaki,Michail Orfanakis,Eirini Dermitzaki,Maria Tzardi

doi:10.3390/md19060312

Abstract

Inflammatory bowel disease is characterized by extensive intestinal inflammation, and therapies against the disease target suppression of the inflammatory cascade. Nutrition has been closely linked to the development and suppression of inflammatory bowel disease, which to a large extent is attributed to the complex immunomodulatory properties of nutrients. Diets containing fish have been suggested to promote health and suppress inflammatory diseases. Even though most of the health-promoting properties of fish-derived nutrients are attributed to fish oil, the potential health-promoting properties of fish protein have not been investigated. Fish sidestreams contain large amounts of proteins, currently unexploited, with potential anti-inflammatory properties, and may possess additional benefits through bioactive peptides and free amino acids. In this project, we utilized fish protein hydrolysates, based on mackerel and salmon heads and backbones, as well as flounder skin collagen. Mice fed with a diet supplemented with different fish sidestream-derived protein hydrolysates (5% w/w) were exposed to the model of DSS-induced colitis. The results show that dietary supplements containing protein hydrolysates from salmon heads suppressed chemically-induced colitis development as determined by colon length and pro-inflammatory cytokine production. To evaluate colitis severity, we measured the expression of different pro-inflammatory cytokines and chemokines and found that the same supplement suppressed the pro-inflammatory cytokines IL-6 and TNFα and the chemokines Cxcl1 and Ccl3. We also assessed the levels of the anti-inflammatory cytokines IL-10 and Tgfb and found that selected protein hydrolysates induced their expression. Our findings demonstrate that protein hydrolysates derived from fish sidestreams possess anti-inflammatory properties in the model of DSS-induced colitis, providing a novel underexplored source of health-promoting dietary supplements.

Highlights

Intestinal homeostasis is to a large extent maintained by a balance between the host immune system, the gut epithelium, dietary metabolites and, importantly, the gut microbiome [1]
To investigate the potential anti-inflammatory effect of fish sidestream-derived protein hydrolysates (Table 1) in acute intestinal inflammation, we used the murine DDS-induced colitis model, which is broadly used as a model of inflammatory bowel disease
We introduced six female mice per group to a diet supplemented with 5% w/w of the respective extract for 10 days to allow mice to become accustomed to the new diet

Summary

Introduction

Intestinal homeostasis is to a large extent maintained by a balance between the host immune system, the gut epithelium, dietary metabolites and, importantly, the gut microbiome [1]. Intestinal inflammation is the basis for a vast number of celiac and bowel pathologies, and manifests symptoms such as diarrhea, abnormal weight loss, fatigue, pain and malnutrition [2,3,4]. It is usually triggered by the combination of tissue damage and inciting environmental factors, such as gut microbes, and dietary components that increase intestinal permeability [5,6]. Dextran sodium sulfate (DSS)-induced colitis is a widely used animal model for the study of intestinal inflammation, as it is able to simulate acute, chronic and relapsing intestinal inflammation by modulating DSS concentration and administration frequency [9]

Objectives

Methods

Results