Schematic illustration of mechanisms of metabolic syndrome with special reference to Toll-like receptor 4 (TLR4) and proinflammatory cytokine signaling. High-fat diet impairs gut barrier to induce bacterial translocation resulting in dysbiosis. At the same time, dysbiosis reduces gut barrier integrity via the metabolites produced by gut bacteria. Additionally, this change activates the immune system to induce lipopolysaccharide (LPS). LPS activates systemic TLR4 to produce proinflammatory cytokines, resulting in low-grade inflammation, which causes insulin resistance. LPS triggers facilitatation to recruit macrophages into adipose tissue, and activates macrophages and adipocytes via TLR4 to induce local inflammation in adipose tissues. Under this condition, macrophages increase lipolysis through the release of proinflammatory cytokines to produce free fatty acids (FFAs). FFAs are delivered and accumulated in distant organs such as the liver and skeletal muscle, which can induce inflammation via TLR4, leading to insulin resistance. Among these FFAs, saturated FAs act as a ligand for TLR4 in both macrophages and adipocytes to increase the secretion of proinflammatory cytokines, which also contribute to insulin resistance. Additionally, insulin resistance at adipose tissue increases lipolysis, leading to increased release of FFAs. At the same time, oxidized low-density lipoprotein (LDL) is produced by oxidative stress induced by metabolic endotoxemia, and also activates TLR4 to produce proinflammatory cytokines, which is associated with insulin resistance. Thus, insulin resistance and inflammation cause a vicious cycle to induce each other via TLR4.
Forest plot of the associations between gastroesophageal reflux disease and psychosocial disorders.
Representative case of different endoscopic preparation grades for patients with achalasia.
Differences in alpha and beta diversity in esophageal microbiome (A) alpha diversity (Shannon index) and (B) beta diversity (Bray-Curtis index) The alpha diversity presented as Shannon index. Each dot represents an individual sample. Pink bars represent pre-peroral endoscopic myotomy (POEM), fluid; green bars represent post-POEM, fluid; blue bars represent pre-POEM, tissue; and purple bars represent post-POEM, tissue. Data are presented as box-and-whisker plots, with whiskers representing the lowest and highest values within 1.5*interquartile range (IQR). Black diamonds indicates the mean of Shannon index. *
Prevalence of non-celiac gluten sensitivity (NCGS) in Korea via the survey: do you think eating food containing flour/wheat affects the occurrence of gastrointestinal symptoms? IBS, irritable bowel syndrome; VAS, visual analog scale.
Evolution of the neurogenic bowel dysfunction (NBD) score before and after transanal irrigation in 4 specific initial NBD categories. “Very minor group” is defined by NBD score ranged from 0 to 6, “Minor group” is defined by score ranging from 7 to 9, “Moderate group” is defined by score ranging from 10 to 13, “Severe group” is defined by NBD score ranging from 14 to 27. Red boxes correspond to the analyzed groups.
J Neurogastroenterol Motil 2022; 28(2): 167~334 
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