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Journal: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society

142

Gastroesophageal reflux disease (GERD) is associated with obesity and hiatal hernia, and often precedes the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EA). Epidemiological studies show that the global prevalence of GERD is increasing. GERD is a multifactorial disease with a complex genetic architecture. Genome-wide association studies (GWAS) have provided initial insights into the genetic background of GERD. The present review summarizes current knowledge of the genetics of GERD and a possible genetic overlap between GERD and BE and EA. The review discusses genes and cellular pathways that have been implicated through GWAS, and provides an outlook on how future molecular research will enhance understanding of GERD pathophysiology.

Concepts: Genetics, Epidemiology, Asthma, Obesity, Gastroenterology, Gastroesophageal reflux disease, Esophageal cancer, Barrett's esophagus

141

Enterochromaffin cells were the first endocrine cells of the gastrointestinal tract to be chemically distinguished, almost 150 years ago. It is now known that the chromaffin reaction of these cells was due to their content of the reactive aromatic amine, 5-hydroxytryptamine (5-HT, also known as serotonin). They have commonly been thought to be a special class of gut endocrine cells (enteroendocrine cells) that are distinct from the enteroendocrine cells that contain peptide hormones. The study by Martin et al. in the current issue of this journal reveals that the patterns of expression of nutrient receptors and transporters differ considerably between chromaffin cells of the mouse duodenum and colon. However, even within regions, chromaffin cells differ; in the duodenum there are chromaffin cells that contain both secretin and 5-HT, cholecystokinin and 5-HT, and all three of secretin, cholecystokinin, and 5-HT. Moreover, the ratios of these different cell types differ substantially between species. And, in terms of function, 5-HT has many roles, including in appetite, motility, fluid secretion, release of digestive enzymes and bone metabolism. The paper thus emphasizes the need to define the many different classes of enterochromaffin cells and relate this to their roles.

Concepts: Protein, Cell, Pancreas, Receptor, Small intestine, Serotonin, Digestion, Enterochromaffin cell

28

Background  Roux-en-Y gastric bypass (RYGB) surgery is very effective in reducing excess body weight and improving glucose homeostasis in obese subjects. Changes in the pattern of gut hormone secretion are thought to play a major role, but the mechanisms leading to both changed hormone secretion and beneficial effects remain unclear. Specifically, it is not clear whether changes in the number of hormone-secreting enteroendocrine cells, or changes in the releasing stimuli, or both, are important. Methods  We estimated numbers of enteroendocrine cells after immunohistochemical staining in fixed tissue samples from rats at 10-11 months after RYGB. Key Results  Numbers of glucagon-like peptide-1 (GLP-1) (L-cells, co-expressing peptide YY (PYY)), cholecystokinin (CCK), neurotensin, and 5-HT-immunoreactive cells were significantly increased in the Roux and common limbs, but not the biliopancreatic limb in RYGB rats compared with sham-operated, obese rats fed high-fat diet, and chow-fed controls. This increase was mostly accounted for by general hyperplasia of all intestinal wall layers of the nutrient-perfused Roux and common limbs, and less to increased density of expression. The number of ghrelin cells in the bypassed stomach was not different among the three groups. Conclusions & Inferences  The findings suggest that the number of enteroendocrine cells increases passively as the gut adapts, and that the increased total number of L- and I-cells is likely to contribute to the higher circulating levels of GLP-1, PYY, and CCK, potentially leading to suppression of food intake and stimulation of insulin secretion. Whether changes in releasing stimuli also contribute to altered circulating levels will have to be determined in future studies.

Concepts: Nutrition, Insulin, Obesity, Bariatric surgery, Gastric bypass surgery, Bariatrics, Duodenum, Beriberi

28

Observational studies suggest that bariatric surgery is the most effective intervention for achieving a significant and durable weight loss. In patients with type 2 diabetes, such surgery is often associated with remission of their diabetes. The mechanism(s) by which surgeries such as Roux-en-Y Gastric Bypass (RYGB) leads to favorable effects on glucose metabolism remain unknown. RYGB is associated with altered secretion of enteroendocrine hormones, leading to the belief that these hormones contribute to the improvement in insulin secretion and action as well as satiation after this procedure. However, it is important to consider the not insignificant effects of caloric restriction and the mechanical changes to the upper gut in determining the outcomes of such surgery.

Concepts: Insulin, Diabetes mellitus, Obesity, Surgery, Bariatric surgery, Gastric bypass surgery, Bariatrics, Duodenum

26

The Chicago Classification (CC) of esophageal motility disorders, utilizing an algorithmic scheme to analyze clinical high-resolution manometry (HRM) studies, has gained acceptance worldwide.

26

Impaired 5-HT3 receptor function is likely involved in the pathogenesis of functional gastrointestinal disorders (FGID) and 5-HT3 receptor antagonists are effective treatments for chemotherapy-induced nausea and vomiting (CINV) and irritable bowel syndrome (IBS). The monoterpene alcohol menthol and the aporphine alkaloid boldine combat symptoms of gastrointestinal diseases; both interact with other members of the Cys-loop ligand-gated ion channel family and may therefore also act on 5-HT3 receptors.

Concepts: Receptor, Gastroenterology, Ligand, Irritable bowel syndrome, Ion channels, Ligand-gated ion channel, 5-HT3 receptor, Functional colonic disease

25

The neural network mechanisms underlying visceral hypersensitivity in irritable bowel syndrome (IBS) are incompletely understood. It has been proposed that an intrinsic salience network plays an important role in chronic pain and IBS symptoms. Using neuroimaging, we examined brain responses to rectal distension in adolescent IBS patients, focusing on determining the alteration of salience network integrity in IBS and its functional implications in current theoretical frameworks. We hypothesized that (i) brain responses to visceral stimulation in adolescents are similar to those in adults, and (ii) IBS is associated with an altered salience network interaction with other neurocognitive networks, particularly the default mode network (DMN) and executive control network (ECN), as predicted by the theoretical models.

Concepts: Scientific method, Attention, Neuroscience, Cognitive neuroscience, Irritable bowel syndrome, Flatulence, Fibromyalgia, Default network

25

The role that probiotics play in relieving irritable bowel syndrome (IBS) has been demonstrated; however, the mechanism by which IBS is affected remains unclear. In this study, serotonin transporter (SERT) mRNA and serotonin transporter protein (SERT-P) levels in HT-29, Caco-2 cells, and mice intestinal tissues were examined after treatment with Lactobacillus rhamnosus GG supernatant (LGG-s).

Concepts: Bacteria, Constipation, Irritable bowel syndrome, Flatulence, Probiotic, Lactobacillus, Lactobacillus rhamnosus, Serotonin transporter

24

Functional gastrointestinal disorders (FGIDs) are a common, diverse group of disorders of unknown etiology, resulting in significant socieconomic burden. In this study, we aimed to assess the prevalence of FGIDs in children aged 6-18 years and examine their association with various demographic and socioeconomic parameters.

Concepts: Gastroenterology, Child, The Child, Roman Empire, Latin alphabet, Functional colonic disease, Digestive disease

24

Infantile colic is a frequent problem in neonates and infants. This review addresses current management including the results for nutrient modifications; soy-based formulas; and prebiotics, probiotics, and synbiotics.

Concepts: Infant, Pediatrics, Probiotic, Colic, Baby colic