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

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.

Colon Expression of Chemokines and Their Receptors Depending on the Stage of Colitis and Oat Beta-Glucan Dietary Intervention—Crohn’s Disease Model Study

“…In addition, our study analyzed the influence of beta-glucans on the gene expression of important proteins involved in the pathogenesis of IBD. The results of this study, as well as that of the previously published works, confirm the immunomodulatory properties of both oat beta-glucan fractions [32,44,47]. However, high-molar-mass oat beta-glucan showed a stronger effect on the analyzed parameters and decreased the gene expression of Ccl3, Ccl4, Cxcl1, Cxcl2, Ccr1, Ccr2, Ccr5, Cxcr2, Osm, Csf3, and Spp1 in acute inflammation of the colon wall, and the gene expression of Ccl5, Cxcl1, Cxcl2, Cxcl11, Ccr2, Ccr5, Cxcr2, and Spp1 in the preremission phase (Table 1).…”

“…Activation of this pathway can induce multiple G protein-mediated signaling cascades, including phosphatidylinositol-3 kinase (PI3K)/Akt, phospholipase C (PLC)/protein kinase C (PKC), and mitogen-activated protein kinase (MAPK)/p38 pathways, as well as Janus kinase (JAK2)/signal transducer and activator of transcription (STAT3) signaling pathway [12]. Activation of these pathways has an antiapoptotic effect and increases cell proliferation, which correlates with the antiapoptotic effect of oat beta-glucans observed in the same animals, especially after 7 days of colitis induction [47].…”

Anti-Inflammatory Activity of Oat Beta-Glucans in a Crohn’s Disease Model: Time- and Molar Mass-Dependent Effects

“…The activation of both types of receptors is different in the acute and remission phase of CD. Dietary intake of βGl and βGh diminished colitis by the time-dependent modulation of autophagy and apoptosis, which involved TLRs (TLR4, TLR5) and Dectin-1 receptor activation, with βGI having a stronger effect on apoptosis (Caspase 3 expression) and βGh on autophagy (LC3B expression) [ 49 ]. Therefore, this might explain the difference in the effect of feeding with beta-glucans during 3 or 7 days after TNBS administration.…”

“…Probably, the mechanism of the immunomodulatory effect of beta-glucans may also depend on its molar mass, which influences the severity of apoptosis and autophagy of colon epithelial cells. Our previous results show the most prominent reduction of mucosa and submucosa lymphocytes infiltration occurred after dietary supplementation with high molecular mass oat beta-glucan, while in the case of potential for the improvement of the cytokine gene and protein level, low molecular mass oat beta-glucan was more potent [ 43 , 49 ]. Beta-glucans with different molar mass activate different signaling pathways, and consequently, both forms reduce inflammation and accelerate remission, including restoration of integrity of the intestinal barrier [ 49 ].…”

Beta-Glucan in Foods and Health Benefits

“…Structural studies report that combinations of β-1,3 and β-1,6 bonds form long linear β-glucans, and these structures can be detected by specific intestinal receptors, such as dectin-1, which then stimulate the immunological system [ 1 ]. Cereal β-glucans that have been derived from barley and oats have also been widely researched in both animal and human studies [ 2 , 3 , 4 , 5 ]. They are water soluble, viscous polysaccharides with a linear structure in which glucose is bound through β-1,4 and β-1,3 linkages.…”