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. 2022 Mar 28;13(5):1628–1651. doi: 10.1093/advances/nmac029

FIGURE 1.

FIGURE 1

Potential mechanisms of proinflammatory diets on IBD. The Western diet not only increases the permeability of the epithelial barrier by inhibiting the expression of mucin 2 and upregulating the concentrations of TLRs and LPS, but also activates the mTOR, which further causes intestinal dysfunction and the excessive release of proinflammatory cytokines, and the inflammatory response further disrupts the balance between Treg and Th17 cells in the intestine, ultimately leading to an increased risk of IBD. The high-glucose diet increases the permeability of the epithelial barrier and the sensitivity of proinflammatory cytokines, and activates TGF-β by upregulating the production of ROS in T cells, thereby promoting the differentiation of Th17 cells and ultimately triggering IBD. The high-fat diet could increase oxidative stress in the ER of goblet cells and decrease the expression of mucin 2 and claudin1, thereby disrupting the intestinal barrier and triggering an inflammatory response, and further disrupting the balance between NK T and Treg cells, ultimately exacerbating IBD. The high-salt diet could destroy the colonic barrier by reducing the expression of mucin 2, occluding, and ZO1, which induces excessive release of proinflammatory cytokines, thereby activating the p38/MAPK signaling pathway, disrupting the balance between Treg and Th17 cells and ultimately aggravating IBD. In addition, p38/MAPK can activate SGK1, which promotes the accumulation of salt in the colon via epithelial sodium channels (ENaC) and triggers a proinflammatory “vicious cycle.” →: Pro; ┤: Anti. ENaC, epithelial sodium channels; ER, endoplasmic reticulum; IBD, inflammatory bowel disease; MLKL, mixed lineage kinase domain like pseudokinase; mTOR, mammalian target of rapamycin; Na+, sodium; NFAT5, nuclear factor of activated T cells 5; NK T cells, natural killer T cells; P, phosphorylate; p38/MAPK, p38/mitogen-activated protein kinase; RIPK3, receptor-interacting serine-threonine kinase 3; RORC, retinoic-acid-related orphan nuclear receptor C; RORγt, retinoid-related orphan nuclear receptor γ t; ROS, reactive oxygen species; SGK1, serum glucocorticoid kinase 1; TGF-β, transforming growth factor-β; Th17, T helper 17 cells; TLR, Toll-like receptor; Treg, regulatory T cells; TRIM11, tripartite motif containing 11; ZO1, zonula occludens 1.