American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for "IBS mimickers" such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism.

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome.

Irritable bowel syndrome (IBS), which is characterized by recurrent abdominal pain and disordered bowel habits, is one of the most common functional bowel disorders. IBS is a substantial burden on both patient health-related quality of life and healthcare costs. Several pathophysiologic mechanisms have been postulated for the occurrence of IBS, including altered gastrointestinal motility, visceral hypersensitivity, changes in gut permeability, immune activation, gut-brain dysregulation, central nervous system dysfunction, and changes in the gut microbiota. Of note, both qualitative and quantitative differences have been observed in the gut microbiota of a population with IBS versus a healthy population. Because of the substantial interest in the gut microbiota and its role as a therapeutic target in IBS, this article provides an overview of specific interventions with the potential to modulate the gut microbiota in IBS, including elimination diets, prebiotics, probiotics, synbiotics, and nonsystemic antibiotics. Although probiotics and synbiotics are generally well tolerated, differences in the composition and concentration of different bacterial species and inclusion or exclusion of prebiotic components varies widely across studies and has prevented strong recommendations on their use in IBS. For nonsystemic antibiotics, rifaximin is indicated in the United States for the treatment of IBS with diarrhea in adults and has been shown to be efficacious and well tolerated in well-designed clinical trials. Overall, more consistent evidence is needed regarding the efficacy and safety of elimination diets, prebiotics, probiotics, and synbiotics for the treatment of patients with IBS. Furthermore, additional well-designed studies are needed that examine alterations in the gut microbiota that occur with these interventions and their potential associations with clinical symptoms of IBS.

Irritable bowel syndrome and chronic constipation: emerging drugs, devices, and surgical treatments.

Irritable bowel syndrome (IBS) and chronic constipation (CC) are two of the most common functional disorders of the gut. CC and IBS are estimated to affect up to 20% and 27% of the North American population respectively. Although not life-threatening, CC and IBS can profoundly and negatively affect quality of life and are associated with a significant economic burden related to direct and indirect annual health-care costs. Possible etiologies for IBS and CC include alterations in visceral sensation and gastrointestinal motility. IBS may be caused by disturbances in brain-gut interactions affecting gastrointestinal motility and visceral sensitivity. Research efforts in CC have begun to identify abnormalities in myenteric neurons, alterations in neurotransmitters and their receptors, and incoordination of the muscles of the pelvic floor or anorectum. Both disorders may be influenced by genetic predisposition, environmental factors, and stress. In this article, the safety and efficacy of traditional and emerging therapies for CC and IBS are examined. In addition, their pathophysiology and symptoms are briefly reviewed.

Irritable bowel syndrome: new and emerging therapies.

PURPOSE OF REVIEW: Irritable bowel syndrome refers to abdominal discomfort associated with altered bowel habits. Recent evidence suggests that the primary pathophysiologic mechanism is brain-gut dysregulation. Many central and peripheral factors are involved. This article will review important pathophysiologic mechanisms with a focus on new and emerging therapies. RECENT FINDINGS: Prior gastroenteritis and small intestinal bacterial overgrowth may be important for treatment of irritable bowel syndrome. Understanding of serotonergic receptors in gastrointestinal function has led to the development of serotonergic agents such as alosetron and tegaserod. Novel agents targeting other receptor sites include neurokinin and neurohormonal modulators, chloride channels and opioid receptors. Other therapeutic approaches - behavioral treatments, probiotics, antibiotics and alternative therapies - have developing roles in the treatment of irritable bowel syndrome. SUMMARY: A better understanding of pathophysiologic mechanisms has resulted in therapeutic advances. Prokinetic therapies may have a role in nondiarrhea predominant irritable bowel syndrome. Antidepressants are used to modulate pain and treat comorbid psychological distress. Newer agents target various receptor sites. Advances in psychological/behavioral treatments and alternative modalities hold promise for the future.