Eckol alleviates intestinal dysfunction during suckling-to-weaning transition via modulation of PDX1 and HBEGF

Abstract

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

The Impact of Weaning Stress on Gut Health and the Mechanistic Aspects of Several Feed Additives Contributing to Improved Gut Health Function in Weanling Piglets—A Review

“…Yuan et al [ 95 ] reported that by the dietary inclusion of flavones extracted from the leaves of Eucommia ulmoides enhanced intestinal morphology and integrity of diquat challenged pigs via improved intestinal barrier function. In addition, several other studies reported that supplementation of plant extract alone or in combination improved performance, digestibility, and intestinal barrier function in weaning pigs [ 77 , 78 , 79 ]. Ecklonia species (commonly known as brown algae) possessing a wide range of therapeutic properties, and enriched with vitamins, minerals, dietary fiber, proteins, and polysaccharide have received considerable attention in recent decades.…”

“…In addition to this, a linear increase in overall average daily gain and feed efficiency ( Figure 1 ) in weaning pigs has been reported by Choi et al [ 96 ]. To evaluate the molecular mechanism of how eckol mitigate intestinal dysfunction, the changes in gene expression and intestinal function after Eckol treatment during the suckling-to-weaning transition were evaluated by Lee and Kim [ 79 ]. These authors investigated the biological roles of differentially expressed genes (DEGs) in intestinal development by assessing intestinal wound healing and barrier functions, as well as the associated signaling pathways and oxidative stress levels.…”

“…An in vivo trial with eckol in weaning pigs altered the gene expression in intestinal samples and the expression patterns were confirmed in the small intestine. Furthermore, according to Lee and Kim [ 79 ], treating the IPEC-J2 intestinal porcine enterocyte cell line with different concentrations ranging from 10 to 200 μM of eckol and incubating for 24 h resulted in a concentration-dependent increase in pancreatic and duodenal homeobox (PDX)1, and heparin-binding EGF-like growth factor (HBEGF) mRNA and protein levels. Additionally, eckol alleviated H 2 O 2 -induced oxidative stress through PI3K/AKT, P38, and 5′-AMP-activated protein kinase (AMPK) signaling pathways.…”