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Chronic idiopathic constipation is highly prevalent among adults. Bile acids (BAs) and the enterohepatic BA circulation modulate colonic secretion and motility that affect transit. BAs in the colon have a dual action as osmotic and stimulant agents. Newer agents, such as elobixibat (A3309), an inhibitor of the ileal BA transporter, have the potential to improve significantly the management of chronic constipation, with minimal adverse effects. Elobixibat modulates the enterohepatic BA circulation, enhancing the delivery of BAs to the colon where they induce secretory and motor effects. Secondary effects of the inhibition of BA absorption are reduced activation of the farnesoid X receptor, decreased secretion of fibroblast growth factor-19 into the portal circulation, and increased BA synthesis. This review focuses on the role of BAs, the enterohepatic BA circulation, and an ileal BA transporter inhibitor (elobixibat) in chronic constipation.

AbstractThe gastrointestinal tract is a vast neuroendocrine organ with extensive extrinsic and intrinsic neural circuits that interact to control its function. Circulating and paracrine hormones (amine and peptide) provide further control of secretory, absorptive, barrier, motor and sensory mechanisms that are essential to the digestion and assimilation of nutrients, and the transport and excretion of waste products. Specialized elements of the mucosa (including enteroendocrine cells, enterocytes and immune cells) and the microbiome interact with other intraluminal contents derived from the diet, and with endogenous chemicals that alter the gut's functions. The totality of these control mechanisms is often summarized as the brain–gut axis. In irritable bowel syndrome (IBS), which is the most common gastrointestinal disorder, there may be disturbances at one or more of these diverse control mechanisms. Patients present with abdominal pain in association with altered bowel function. This review documents advances in understanding the pathophysiological mechanisms in the brain–gut axis in patients with IBS. It is anticipated that identification of one or more disordered functions in clinical practice will usher in a renaissance in the management of IBS, leading to effective therapy tailored to the needs of the individual patient.

Obesity is a complex disease that results from increased energy intake and decreased energy expenditure. The gastrointestinal system plays a key role in the pathogenesis of obesity and facilitates caloric imbalance. Changes in gastrointestinal hormones and the inhibition of mechanisms that curtail caloric intake result in weight gain. It is not clear if the gastrointestinal role in obesity is a cause or an effect of this disease. Obesity is often associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Obesity is also associated with gastrointestinal disorders, which are more frequent and present earlier than T2DM and CVD. Diseases such as gastroesophageal reflux disease (GERD), cholelithiasis, or nonalcoholic steatohepatitis are directly related to body weight and abdominal adiposity. Our objective is to assess the role of each gastrointestinal organ in obesity and the gastrointestinal morbidity resulting in those organs from the effects of obesity.

BackgroundHenoch‐Schönlein purpura (HSP) is a vasculitis that can affect the skin and kidneys. It is characterized by immunoglobulin (Ig) A‐predominant deposition in small blood vessels. To our knowledge, there has been no comparison of direct immunofluorescence (DIF) findings in skin and kidney biopsy specimens.MethodsWe retrospectively studied 21 adults with HSP who had IgA deposition in the skin and kidneys. The skin and kidney DIF findings were compared and tested for an association with the progression of renal disease.ResultsMean age of the patients was 51.4 years. Follow‐up data were available for 19 patients, of whom 5 had progression to chronic kidney disease or renal failure. Concordance between DIF findings on skin and renal biopsies was 100% for IgA, 80% for C3, 80% for IgG, 71% for IgM and 53% for fibrinogen. A worse renal outcome was associated with renal IgG deposition (p = 0.04). A trend for worse renal outcome was found with renal fibrinogen and skin IgM deposition (p = 0.10 and 0.14, respectively).ConclusionsIn this retrospective study of adult HSP, the concordance between DIF findings in skin and kidney specimens was low‐moderate. Further study is required to elucidate the mechanisms responsible for these differences in Ig deposition.

Abstract Background Gastrointestinal ( GI ) infections resulting from bacterial, viral, and parasitic pathogens predispose to postinfectious irritable bowel syndrome ( PI ‐ IBS ) and other functional GI disorders. Existing literature supports the role of enterochromaffin cell hyperplasia, serotonin synthesis and reuptake, impaired barrier function, altered immune activation, and potentially mast cell activation in the pathophysiology of PI ‐ IBS . Purpose The objective of this review was to summarize from the literature the characteristics of the pathogens commonly implicated in PI ‐ IBS , their acute enteritis phases, and the changes seen in the postinfectious phase that may contribute toward development of IBS . A limitation of our current understanding is that the postinfectious GI sequelae reported in prior studies followed epidemic diarrheal outbreaks often involving more than one pathogen, or the studies focused on highly selected, tertiary referral patients. Understanding the mechanisms, natural history, and optimized management of individuals suffering PI ‐ IBS following the more typical sporadic infection requires larger studies of PI ‐ IBS following GI infections encountered in community settings. These studies should include genetic, physiological, and molecular studies to provide more generalizable information that can ultimately be used to diagnose, manage, and potentially prevent the development of PI ‐ IBS .

Gastroparesis and other types of gastric dysfunction result in substantial morbidity in diabetes patients. The pathophysiology of these disorders is incompletely understood. This article reviews techniques applicable to the assessment of gastric function in diabetes patients, including the measurement of emptying, accommodation, and contractility. Available treatment options are also reviewed, including novel yet unapproved serotonin 5-HT 4 agonist pharmacological treatments, as well as the role of endoscopic, surgical, and device treatments of gastroparesis.

Despite advances in understanding the roles of adiposity, food intake, GI and adipocyte-related hormones, inflammatory mediators, the gut–brain axis and the hypothalamic nervous system in the pathophysiology of obesity, the effects of different therapeutic interventions on those pathophysiological mechanisms are controversial. There are still no low-cost, safe, effective treatments for obesity and its complications. Currently, bariatric surgical approaches targeting the GI tract are more effective than non-surgical approaches in inducing weight reduction and resolving obesity-related comorbidities. However, current guidelines emphasise non-surgical approaches through lifestyle modification and medications to achieve slow weight loss, which is not usually sustained and may be associated with medication-related side effects. This review analyses current central, peripheral or hormonal targets to treat obesity and addresses challenges and opportunities to develop novel approaches for obesity.

BackgroundPatients with disorders of gastrointestinal function may undergo unnecessary treatment if misdiagnosed as motility disorders.ObjectiveTo report on clinical features, medical, surgical, and psychiatric comorbidities, and prior treatments of a patient cohort diagnosed concurrently with nonpsychogenic rumination syndrome and pelvic floor dysfunction (also termed rectal evacuation disorder).MethodsFrom a consecutive series (1994–2013) of 438 outpatients with rectal evacuation disorders in the practice of a single gastroenterologist at a tertiary care centre, 57 adolescents or adults were diagnosed with concomitant rumination syndrome. All underwent formal psychological assessment or completed validated questionnaires.ResultsAll 57 patients (95% female) fulfilled Rome III criteria for rumination syndrome; rectal evacuation disorder was confirmed by testing of anal sphincter pressures and rectal balloon evacuation. Prior to diagnosis, most patients underwent multiple medical and surgical treatments (gastrostomy, gastric fundoplication, other gastric surgery, ileostomy, colectomy) for their symptoms. Psychological comorbidity was identified in 93% of patients. Patients were managed predominantly with psychological and behavioural approaches: diaphragmatic breathing for rumination and biofeedback retraining for pelvic floor dysfunction.ConclusionsAwareness of concomitant rectal evacuation disorder and rumination syndrome and prompt identification of psychological comorbidity are keys to instituting behavioural and psychological methods to avoid unnecessary treatment.

SummaryBackgroundHighly selective 5‐HT4agonists have been suggested for the treatment of chronic constipation (CC).AimTo assess the effects of highly selective 5‐HT4agonists (prucalopride, velusetrag or naronapride) on patient‐important clinical efficacy outcomes and safety in adults withCC.MethodsWe searched the medical literature in January 2013 usingMEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5‐HT4agonists in adults withCC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention‐to‐treat analyses, pooled using a random‐effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI).ResultsMain outcomes included stool frequency, Patient‐Assessment of Constipation Quality of Life (PAC‐QOL),PACof symptoms (PAC‐SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5‐HT4agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95%CI1.23–2.79); mean ≥1SCBMover baseline (RR = 1.57; 95%CI1.19, 2.06); ≥1 point improvement inPAC‐QOLandPAC‐SYMscores. The only active comparator trial of prucalopride andPEG3350 suggestedPEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5‐HT4agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride.ConclusionDemonstration of efficacy on patient‐important outcomes and a favourable safety profile support the continued use and development of highly selective 5–HT4agonists in the treatment of chronic constipation.