Eckol Alleviates Intestinal Dysfunction during Suckling-to-Weaning Transition via Modulation of PDX1 and HBEGF.

Sang In Lee,In Ho Kim

doi:10.3390/ijms21134755

Abstract

Maintaining intestinal health in livestock is critical during the weaning period. The precise mechanisms of intestinal dysfunction during this period are not fully understood, although these can be alleviated by phlorotannins, including eckol. This question was addressed by evaluating the changes in gene expression and intestinal function after eckol treatment during suckling-to-weaning transition. The biological roles of differentially expressed genes (DEGs) in intestinal development were investigated by assessing intestinal wound healing and barrier functions, as well as the associated signaling pathways and oxidative stress levels. We identified 890 DEGs in the intestine, whose expression was altered by eckol treatment, including pancreatic and duodenal homeobox (PDX)1, which directly regulate heparin-binding epidermal growth factor-like growth factor (HBEGF) expression in order to preserve intestinal barrier functions and promote wound healing through phosphoinositide 3-kinase (PI3K)/AKT and P38 signaling. Additionally, eckol alleviated H2O2-induced oxidative stress through PI3K/AKT, P38, and 5’-AMP-activated protein kinase (AMPK) signaling, improved growth, and reduced oxidative stress and intestinal permeability in pigs during the weaning period. Eckol modulates intestinal barrier functions, wound healing, and oxidative stress through PDX/HBEGF, and improves growth during the suckling-to-weaning transition. These findings suggest that eckol can be used as a feed supplement in order to preserve the intestinal functions in pigs and other livestock during this process.

Highlights

The suckling-to-weaning transition contributes to intestinal dysfunction in livestock, which undermines animal health, growth, and feed intake [1]
The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the proteins were mainly associated with the following categories: cytokine–cytokine receptor, neuroactive ligand–receptor, and extracellular matrix–receptor interactions; peroxisome proliferator–activated receptor γ, chemokine, Janus kinase-signal transducer and activator of transcription (STAT), tumor necrosis factor, Toll-like receptor, and transforming growth factor (TGF)-β signaling; inflammatory bowel disease (IBD); and, retinol metabolism (Supplemental Table S4)
We found that eckolinduced PDX1 activates heparin-binding epidermal growth factor-like growth factor (HBEGF) expression, which is implicated in wound healing, heart development, and gut protection [34,35,36]

Summary

Introduction

The suckling-to-weaning transition contributes to intestinal dysfunction in livestock, which undermines animal health, growth, and feed intake [1]. The intestinal epithelium is composed of single-layered columnar epithelial cells that are sealed by junctional complexes, including tight and adherens junctions, in close proximity to the apical and lateral sides of the paracellular space [5] It functions as a barrier against harmful substances, including pathogenic bacteria and food allergens [6]. Many alternatives, including probiotics, organic acids, and polyphenols, are used as substitutes due to a ban on antibiotic use in feedstuffs, in-feed antibiotics are used to reduce weaning-induced stress and enhance growth performance [12,13,14] Among these candidates, polyphenols may have the greatest potential to enhance gut intestinal health [15]

Methods

Results

Conclusion