• adipokine
• clinical symptoms
• irritable bowel syndrome
• omentin-1
• psychological symptoms
• quality of life

• Electroacupuncture
• Irritable bowel syndrome
• Transcutaneous electrical acustimulation
• Visceral pain

• enteric neurons
• irritable bowel syndrome
• mast cells
• mastocytosis
• neuroimaging
• small bowel

• Irritable bowel syndrome
• Mast cell activation syndrome
• Mast cell enterocolitis
• Mast cells
• Systemic mastocytosis

• Humans
• Mast Cells/pathology
• Mast Cells/physiology
• Gastrointestinal Tract/pathology
• Mastocytosis/diagnosis
• Mastocytosis/pathology
• Mastocytosis, Systemic/pathology
• Biopsy

• Adenosine 2A receptor
• Irritable bowel syndrome
• Post-infectious irritable bowel syndrome
• Regulation
• Signaling pathway
• γδ T cells

• Mice
• Animals
• Irritable Bowel Syndrome
• NF-kappa B/metabolism
• Interleukin-17/metabolism
• Interleukin-6
• Cytokines/metabolism
• Signal Transduction
• Trichinellosis/complications
• Inflammation/complications
• Interleukin-1

• irritable bowel syndrome
• mast cell activation syndrome
• mastocytic enterocolitis
• systemic mastocytosis

Irritable bowel syndrome (IBS) is characterized with abdominal pain, bloating, and changes in bowel habits, and dealing with IBS is still a clinical challenge. The pathogenesis of IBS has been reported to be linked to low-grade mucosal inflammation, and macrophages contribute to the pathological process of this disease. Kurarinone (KAR), a flavanoid derived from Sophora flavescens, has been found medically effective in many inflammatory conditions and cancers. KAR was previously reported to inhibit LPS-induced expression of inflammatory cytokines in macrophages, whether and how KAR regulates the functions of macrophage in IBS remains to be elusive.

We established a TNBS-induced IBS mouse model, in which KAR was administrated, and mucosal cytokine expression was measured by qRT-PCR. Additionally, mouse macrophages were generated in vitro and their responses to LPS were evaluated by flow cytometry and qRT-PCR. AhR^+/+ or AhR^−/- macrophages were transferred into DTx-treated CD11b-DTR transgenic mice to investigate the role of AhR in IBS. We collected colonic biopsies and peripheral blood samples from 64 patients with IBS, and analyzed AhR expression by qRT-PCR.

We found KAR effectively alleviated visceral hypersensitivity and maintained intestinal barrier functions in mice with IBS. KAR inhibited LPS-induced macrophage activation and expression of pro-inflammatory genes, while increased anti-inflammatory gene expression including IL-10 in an AhR-dependent manner. Using macrophage-depleted mice, we found that chimera mice with AhR^−/- macrophages were more susceptible to TNBS-induced IBS and the therapeutic effect of KAR on IBS was significantly impaired in mice with AhR^−/- macrophages. Additionally, we found AhR expression in macrophages of IBS patients was associated with the disease severity.

Our findings provide new evidences that KAR regulates IBS development via macrophage-intrinsic AhR. KAR might show promise as an immunomodulatory therapeutic agent in treating IBS.

• aryl hydrocarbon receptor
• flavonoid
• irritable bowel syndrome
• kurarinone
• macrophage

Background and objectives: Duodenal lymphocytosis (DL) is a condition characterized by enhanced infiltration of intraepithelial lymphocytes (IELs) in the duodenal mucosa, and it can be linked to both gluten- and non-gluten-related diseases, such as irritable bowel syndrome (IBS). Materials and methods: We retrospectively selected patients with DL linked to IBS. Formalin-embedded biopsy samples of the duodenum were collected. CD3 lymphocyte immunohistochemistry was used for IELs. The real-time polymerase chain reaction was used to quantify the amount of mRNA coding for tissue transglutaminase 2 (tTG2), interferon-gamma (IFNγ), toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88). All subjects underwent DQ2-8 haplotype analysis. Controls were represented by subjects with IBS without DL. Results: Thirty-two patients with IBS-DL were retrospectively recruited. Fourteen subjects (43.8%) had a DQ2-8 haplotype. DQ2-8 positive subjects had similar levels compared to negative ones for tTG2, IFNγ, TLR2, and MyD88. Cigarette smoke did not influence molecular expression in our study. Smokers had a statistically higher IELs count than non-smokers (54.2 ± 7.7 vs. 36.0 ± 8.8, p < 0.001). A significant, direct correlation between IELs and duodenal expression of IFNγ was found (r = 0.36, p = 0.04). Conclusions: IBS with DL showed higher expression of inflammatory markers than controls, but DQ2-8 haplotype did not seem to affect their expression. Smoking might increase IELs infiltration.

• duodenal lymphocytosis
• inflammation
• intraepithelial lymphocytes
• irritable bowel syndrome
• smoking

• B-Lymphocytes/immunology
• Colon/immunology
• Duodenum/immunology
• Dyspepsia/immunology
• Eosinophilia/immunology
• Gastrointestinal Diseases/immunology
• Humans
• Irritable Bowel Syndrome/immunology
• Lymphocyte Activation/immunology
• Lymphocyte Count
• Mast Cells/immunology
• T-Lymphocytes/immunology
• Th17 Cells
• Th2 Cells

• Children
• Constipation
• Cytokine
• Inflammation
• Neopterin

• Irritable bowel syndrome
• cytokines
• innate immunity
• low-grade inflammation
• toll-like receptors

• colonic biopsies
• immunity
• irritable bowel syndrome
• lymphocytes
• mast cell

• CD3 Complex/metabolism
• CD4-Positive T-Lymphocytes/metabolism
• CD8-Positive T-Lymphocytes/metabolism
• Colon/immunology
• Humans
• Irritable Bowel Syndrome/immunology
• Mast Cells/metabolism

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal (GI) disorder that is characterized by a combination of abdominal pain or discomfort, bloating and alterations in bowel movements. This review presents recent developments concerning the roles of diet and GI endocrine cells in the pathophysiology of IBS and of individual dietary guidance in the management of IBS. Patients with IBS typically report that food aggravates their IBS symptoms. The interactions between specific types of foodstuffs rich in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and GI endocrine cells induce changes in cell densities. Providing individual dietary guidance about a low FODMAP intake, high soluble-fiber intake, and changing the proportions of protein, fat and carbohydrates helps to reduce the symptoms experienced by patients with IBS and to improve their quality of life. These improvements are due to restoring the densities of the GI endocrine cells back to normal. The reported observations emphasize the role of GI endocrine cells in the pathophysiology of IBS and support the provision of dietary guidance as a first-line treatment for managing IBS.

• T lymphocyte
• cytokine
• enterochromaffin cell
• interleukin
• irritable bowel syndrome
• mast cell

Irritable bowel syndrome is one of the most common functional gastrointestinal (GI) disorders that significantly impair quality of life in patients. Current available treatments are still not effective and the pathophysiology of this condition remains unclearly defined. Recently, research on intestinal stem cells has greatly advanced our understanding of various GI disorders. Alterations in conserved stem cell regulatory pathways such as Notch, Wnt, and bone morphogenic protein/TGF-β have been well documented in diseases such as inflammatory bowel diseases and cancer. Interaction between intestinal stem cells and various signals from their environment is important for the control of stem cell self-renewal, regulation of number and function of specific intestinal cell types, and maintenance of the mucosal barrier. Besides their roles in stem cell regulation, these signals are also known to have potent effects on immune cells, enteric nervous system and secretory cells in the gut, and may be responsible for various aspects of pathogenesis of functional GI disorders, including visceral hypersensitivity, altered gut motility and low grade gut inflammation. In this article, we briefly summarize the components of these signaling pathways, how they can be modified by extrinsic factors and novel treatments, and provide evidenced support of their roles in the inflammation processes. Furthermore, we propose how changes in these signals may contribute to the symptom development and pathogenesis of irritable bowel syndrome.

• Intestinal stem cells
• Irritable bowel syndrome
• Notch
• Transforming growth factor beta
• Wnt

• chromogranin A
• genes
• low-grade inflammation
• microbiota
• peptide YY
• somatostatin
• stem cell

To determine the large intestinal endocrine cell types affected following dietary guidance in patients with irritable bowel syndrome (IBS).

The study included 13 IBS patients and 13 control subjects. The patients received three sessions of individualized dietary guidance. Both the control subjects and the patients were scheduled for colonoscopies at baseline and again for the patients at 3–9 months after dietary guidance. Biopsy samples were taken from the colon and rectum and were immunostained for all types of large intestinal endocrine cells. The endocrine cells were quantified using computerized image analysis.

The daily total consumption (mean±s.e.m. values) of fruits and vegetables rich in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) decreased significantly from 16.2±5.3 g before receiving dietary guidance to 9.2±3.2 g after receiving dietary guidance (P=0.02). In the total colon, the densities of serotonin cells were 46.8±8.9, 10.5±2.1 and 22.6±3.2 cells/mm² in control subjects and in IBS patients before and after receiving dietary guidance, respectively (P=0.007); the corresponding densities of peptide YY cells were 11.6±1.8, 10.8±1.7 and 16.8±2.1 cells/mm², respectively (P=0.06). The cell densities for both serotonin and peptide YY did not change significantly in the rectum. The densities of somatostatin cells in the rectum were 13.5±3.0, 13.2±3.0, and 22.3±3.2 cells/mm² for control subjects and for IBS patients before and after receiving dietary guidance, respectively (P=0.01).

The densities of the large intestinal endocrine cells tend to normalize following dietary guidance that may have contributed to the improvement of the patients with IBS symptoms.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.

• Diet
• Endocrine cells
• Genetic factors
• Low-grade inflammation
• Microbiota
• Stem cells

• Animals
• Comorbidity
• Diet/adverse effects
• Gene-Environment Interaction
• Genetic Markers
• Genetic Predisposition to Disease
• Host-Pathogen Interactions
• Humans
• Intestines/microbiology
• Intestines/pathology
• Intestines/physiopathology
• Irritable Bowel Syndrome/etiology
• Irritable Bowel Syndrome/genetics
• Irritable Bowel Syndrome/metabolism
• Irritable Bowel Syndrome/microbiology
• Irritable Bowel Syndrome/physiopathology
• Microbiota
• Phenotype
• Risk Factors
• Signal Transduction
• Stem Cells/metabolism
• Stem Cells/microbiology
• Stem Cells/pathology

• Adult
• Case-Control Studies
• Colitis, Ulcerative/immunology
• Colon/cytology
• Colon/immunology
• Colon/pathology
• Female
• Health Surveys
• Humans
• Intestinal Mucosa/cytology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/pathology
• Irritable Bowel Syndrome/immunology
• Male
• Middle Aged
• Quality of Life
• Surveys and Questionnaires

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, characterized by abdominal pain, bloating, and changes in bowel habits. These symptoms cannot be explained by structural abnormalities and there is no specific laboratory test or biomarker for IBS. Therefore, IBS is classified as a functional disorder with diagnosis dependent on the history taking about manifested symptoms and careful physical examination. Although a great deal of research has been carried out in this area, the pathophysiology of IBS is complex and not completely understood. Multiple factors are thought to contribute to the symptoms in IBS patients; altered gastrointestinal motility, visceral hypersensitivity, and the brain-gut interaction are important classical concepts in IBS pathophysiology. New areas of research in this arena include inflammation, postinfectious low-grade inflammation, genetic and immunologic factors, an altered microbiota, dietary factors, and enteroendocrine cells. These emerging studies have not shown consistent results, provoking controversy in the IBS field. However, certain lines of evidence suggest that these mechanisms are important at least a subset of IBS patients, confirming that IBS symptoms cannot be explained by a single etiological mechanism. Therefore, it is important to keep in mind that IBS requires a more holistic approach to determining effective treatment and understanding the underlying mechanisms.

• Pathophysiology
• Irritable bowel syndrome
• Inflammation
• Immunologic
• Genetics
• Microbiota
• Diet
• Enteroendocrine cell

• Animals
• Diet/adverse effects
• Enteroendocrine Cells/metabolism
• Genetic Predisposition to Disease
• Humans
• Inflammation Mediators/metabolism
• Intestinal Mucosa/metabolism
• Intestines/immunology
• Intestines/innervation
• Intestines/microbiology
• Intestines/physiopathology
• Irritable Bowel Syndrome/genetics
• Irritable Bowel Syndrome/immunology
• Irritable Bowel Syndrome/metabolism
• Irritable Bowel Syndrome/microbiology
• Irritable Bowel Syndrome/physiopathology
• Phenotype
• Prognosis
• Risk Factors
• Signal Transduction