Effects of Dietary Oat Beta-Glucans on Colon Apoptosis and Autophagy through TLRs and Dectin-1 Signaling Pathways-Crohn's Disease Model Study

Nutrients. 2021 Jan 22;13(2):321. doi: 10.3390/nu13020321.

Abstract

Background: Crohn's disease (CD) is characterized by chronic inflammation of the gastrointestinal tract with alternating periods of exacerbation and remission. The aim of this study was to determine the time-dependent effects of dietary oat beta-glucans on colon apoptosis and autophagy in the CD rat model.

Methods: A total of 150 Sprague-Dawley rats were divided into two main groups: healthy control (H) and a TNBS (2,4,6-trinitrobenzosulfonic acid)-induced colitis (C) group, both including subgroups fed with feed without beta-glucans (βG-) or feed supplemented with low- (βGl) or high-molar-mass oat beta-glucans (βGh) for 3, 7, or 21 days. The expression of autophagy (LC3B) and apoptosis (Caspase-3) markers, as well as Toll-like (TLRs) and Dectin-1 receptors, in the colon epithelial cells, was determined using immunohistochemistry and Western blot.

Results: The results showed that in rats with colitis, after 3 days of induction of inflammation, the expression of Caspase-3 and LC3B in intestinal epithelial cells did not change, while that of TLR 4 and Dectin-1 decreased. Beta-glucan supplementation caused an increase in the expression of TLR 5 and Dectin-1 with no changes in the expression of Caspase-3 and LC3B. After 7 days, a high expression of Caspase-3 was observed in the colitis-induced animals without any changes in the expression of LC3B and TLRs, and simultaneously, a decrease in Dectin-1 expression was observed. The consumption of feed with βGl or βGh resulted in a decrease in Caspase-3 expression and an increase in TLR 5 expression in the CβGl group, with no change in the expression of LC3B and TLR 4. After 21 days, the expression of Caspase-3 and TLRs was not changed by colitis, while that of LC3B and Dectin-1 was decreased. Feed supplementation with βGh resulted in an increase in the expression of both Caspase-3 and LC3B, while the consumption of feed with βGh and βGl increased Dectin-1 expression. However, regardless of the type of nutritional intervention, the expression of TLRs did not change after 21 days.

Conclusions: Dietary intake of βGl and βGh significantly reduced colitis by time-dependent modification of autophagy and apoptosis, with βGI exhibiting a stronger effect on apoptosis and βGh on autophagy. The mechanism of this action may be based on the activation of TLRs and Dectin-1 receptor and depends on the period of exacerbation or remission of CD.

Keywords: Crohn’s disease; Dectin-1; TLRs; apoptosis; autophagy; colitis; oat beta-glucan; rats.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Autophagy / drug effects
  • Caspase 3 / metabolism
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Crohn Disease / drug therapy*
  • Crohn Disease / etiology
  • Crohn Disease / pathology
  • Cytokines / metabolism
  • Dietary Supplements
  • Disease Models, Animal
  • Inflammation
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Lectins, C-Type / drug effects*
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Toll-Like Receptors / drug effects*
  • beta-Glucans / chemistry
  • beta-Glucans / pharmacology*

Substances

  • Cytokines
  • LC3 protein, rat
  • Lectins, C-Type
  • Microtubule-Associated Proteins
  • Toll-Like Receptors
  • beta-Glucans
  • dectin 1
  • beta-glucan, (1-3)(1-4)-
  • Caspase 3