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Lancet (London, England) Nov 2020Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The... (Review)
Review
Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The condition affects between 5% and 10% of otherwise healthy individuals at any one point in time and, in most people, runs a relapsing and remitting course. The best described risk factor is acute enteric infection, but irritable bowel syndrome is also more common in people with psychological comorbidity and in young adult women than in the rest of the general population. The pathophysiology of irritable bowel syndrome is incompletely understood, but it is well established that there is disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and altered CNS processing. Other less reproducible mechanisms might include genetic associations, alterations in gastrointestinal microbiota, and disturbances in mucosal and immune function. In most people, diagnosis can be made on the basis of clinical history with limited and judicious use of investigations, unless alarm symptoms such as weight loss or rectal bleeding are present, or there is a family history of inflammatory bowel disease or coeliac disease. Once the diagnosis is made, an empathetic approach is key and can improve quality of life and symptoms, and reduce health-care expenditure. The mainstays of treatment include patient education about the condition, dietary changes, soluble fibre, and antispasmodic drugs. Other treatments tend to be reserved for people with severe symptoms and include central neuromodulators, intestinal secretagogues, drugs acting on opioid or 5-HT receptors, or minimally absorbed antibiotics (all of which are selected according to predominant bowel habit), as well as psychological therapies. Increased understanding of the pathophysiology of irritable bowel syndrome in the past 10 years has led to a healthy pipeline of novel drugs in development.
Topics: Abdominal Pain; Brain; Dietary Fiber; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Irritable Bowel Syndrome; Quality of Life
PubMed: 33049223
DOI: 10.1016/S0140-6736(20)31548-8 -
Child and Adolescent Psychiatric... Jul 2020Gastrointestinal disorders are one of the most common medical conditions that are comorbid with autism spectrum disorders. These comorbidities can cause greater severity... (Review)
Review
Gastrointestinal disorders are one of the most common medical conditions that are comorbid with autism spectrum disorders. These comorbidities can cause greater severity in autism spectrum disorder symptoms, other associated clinical manifestations, and lower quality of life if left untreated. Clinicians need to understand how these gastrointestinal issues present and apply effective therapies. Effective treatment of gastrointestinal problems in autism spectrum disorder may result in marked improvements in autism spectrum disorder behavioral outcomes. This article discusses the gastrointestinal disorders commonly associated with autism spectrum disorders, how they present, and studied risk factors.
Topics: Autism Spectrum Disorder; Comorbidity; Diarrhea; Feeding and Eating Disorders; Gastrointestinal Diseases; Humans; Quality of Life
PubMed: 32471598
DOI: 10.1016/j.chc.2020.02.005 -
Lancet (London, England) Nov 2020Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled... (Review)
Review
Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. The pathophysiology of functional gastrointestinal disorders is complex, but involves bidirectional dysregulation of gut-brain interaction (via the gut-brain axis), as well as microbial dysbiosis within the gut, altered mucosal immune function, visceral hypersensitivity, and abnormal gastrointestinal motility. Hence, nomenclature refers to the conditions as disorders of gut-brain interaction. Psychological comorbidity is common; however, whether or not this predates, or is driven by, symptoms is not clear. Patients with functional gastrointestinal disorders can feel stigmatised, and often this diagnosis is not communicated effectively by physicians, nor is education provided. Prompt identification and treatment of these conditions is crucial as they have a considerable impact on health-care systems and society as a whole because of repeated consultations, unnecessary investigations and surgeries, prescriptions and over-the-counter medicine use, and impaired health-related quality of life and ability to work. Symptom-based criteria are used to make a diagnosis, with judicious use of limited investigations in some patients. The general principles of treatment are based on a biopsychosocial understanding and involve management of physical symptoms and, if present, psychological comorbidity. In the future, treatment approaches to functional gastrointestinal disorders are likely to become more personalised, based not only on symptoms but also underlying pathophysiology and psychology.
Topics: Brain; Dyspepsia; Gastrointestinal Diseases; Humans; Irritable Bowel Syndrome; Quality of Life
PubMed: 33049221
DOI: 10.1016/S0140-6736(20)32115-2 -
ELife Feb 2023Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization...
BACKGROUND
Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization (MR) to comprehensively examine associations of smoking and alcohol consumption with common gastrointestinal diseases.
METHODS
Genetic variants associated with smoking initiation and alcohol consumption at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank, FinnGen study, and other large consortia. Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after mutual adjustment for genetic liability to smoking and alcohol consumption.
RESULTS
Genetic predisposition to smoking initiation was associated with increased risk of 20 of 24 gastrointestinal diseases, including 7 upper gastrointestinal diseases (gastroesophageal reflux, esophageal cancer, gastric ulcer, duodenal ulcer, acute gastritis, chronic gastritis, and gastric cancer), 4 lower gastrointestinal diseases (irritable bowel syndrome, diverticular disease, Crohn's disease, and ulcerative colitis), 8 hepatobiliary and pancreatic diseases (non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, liver cancer, cholecystitis, cholelithiasis, and acute and chronic pancreatitis), and acute appendicitis. Fifteen out of 20 associations persisted after adjusting for genetically predicted alcohol consumption. Genetically predicted higher alcohol consumption was associated with increased risk of duodenal ulcer, alcoholic liver disease, cirrhosis, and chronic pancreatitis; however, the association for duodenal ulcer did not remain statistically significant after adjustment for genetic predisposition to smoking initiation.
CONCLUSIONS
This study provides MR evidence supporting causal associations of smoking with a broad range of gastrointestinal diseases, whereas alcohol consumption was associated with only a few gastrointestinal diseases.
FUNDING
The Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Natural Science Foundation of China; Key Project of Research and Development Plan of Hunan Province; the Swedish Heart Lung Foundation; the Swedish Research Council; the Swedish Cancer Society.
Topics: Humans; Mendelian Randomization Analysis; Genetic Predisposition to Disease; Duodenal Ulcer; Smoking; Alcohol Drinking; Esophageal Neoplasms; Liver Diseases, Alcoholic; Gastritis; Pancreatitis, Chronic; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 36727839
DOI: 10.7554/eLife.84051 -
Gastroenterology Jan 2018Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder in the United States, and leads to substantial morbidity, though associated... (Review)
Review
Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder in the United States, and leads to substantial morbidity, though associated mortality is rare. The prevalence of GERD symptoms appeared to increase until 1999. Risk factors for complications of GERD include advanced age, male sex, white race, abdominal obesity, and tobacco use. Most patients with GERD present with heartburn and effortless regurgitation. Coexistent dysphagia is considered an alarm symptom, prompting evaluation. There is substantial overlap between symptoms of GERD and those of eosinophilic esophagitis, functional dyspepsia, and gastroparesis, posing a challenge for patient management.
Topics: Age Factors; Biopsy; Diagnosis, Differential; Dyspepsia; Eosinophilic Esophagitis; Esophageal Neoplasms; Esophagitis, Peptic; Esophagoscopy; Female; Gastroesophageal Reflux; Gastrointestinal Hemorrhage; Gastroparesis; Heartburn; Humans; Male; Obesity; Prevalence; Quality of Life; Risk Factors; Sex Factors; United States
PubMed: 28780072
DOI: 10.1053/j.gastro.2017.07.045 -
Frontiers in Cellular and Infection... 2021Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is associated with visceral hypersensitivity, gut motility, immunomodulation,... (Review)
Review
Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is associated with visceral hypersensitivity, gut motility, immunomodulation, gut microbiota alterations, and dysfunction of the brain-gut axis; however, its pathophysiology remains poorly understood. Gut microbiota and its metabolites are proposed as possible etiological factors of IBS. The aim of our study was to investigate specific types of microbiota-derived metabolites, especially bile acids, short-chain fatty acids, vitamins, amino acids, serotonin and hypoxanthine, which are all implicated in the pathogenesis of IBS. Metabolites-focused research has identified multiple microbial targets relevant to IBS patients, important roles of microbiota-derived metabolites in the development of IBS symptoms have been established. Thus, we provide an overview of gut microbiota and their metabolites on the different subtypes of IBS (constipation-predominant IBS-C, diarrhea-predominant IBS-D) and present controversial views regarding the role of microbiota in IBS.
Topics: Bile Acids and Salts; Fatty Acids, Volatile; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Irritable Bowel Syndrome
PubMed: 34631603
DOI: 10.3389/fcimb.2021.729346 -
Journal of Physiology and Pharmacology... Dec 2011Stress, which is defined as an acute threat to homeostasis, shows both short- and long-term effects on the functions of the gastrointestinal tract. Exposure to stress... (Review)
Review
Stress, which is defined as an acute threat to homeostasis, shows both short- and long-term effects on the functions of the gastrointestinal tract. Exposure to stress results in alterations of the brain-gut interactions ("brain-gut axis") ultimately leading to the development of a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases, food antigen-related adverse responses, peptic ulcer and gastroesophageal reflux disease (GERD). The major effects of stress on gut physiology include: 1) alterations in gastrointestinal motility; 2) increase in visceral perception; 3) changes in gastrointestinal secretion; 4) increase in intestinal permeability; 5) negative effects on regenerative capacity of gastrointestinal mucosa and mucosal blood flow; and 6) negative effects on intestinal microbiota. Mast cells (MC) are important effectors of brain-gut axis that translate the stress signals into the release of a wide range of neurotransmitters and proinflammatory cytokines, which may profoundly affect the gastrointestinal physiology. IBS represents the most important gastrointestinal disorder in humans, and is characterized by chronic or recurrent pain associated with altered bowel motility. The diagnostic testing for IBS patients include routine blood tests, stool tests, celiac disease serology, abdominal sonography, breath testing to rule out carbohydrate (lactose, fructose, etc.) intolerance and small intestinal bacterial overgrowth. Colonoscopy is recommended if alarming symptoms are present or to obtain colonic biopsies especially in patients with diarrhoea predominant IBS. The management of IBS is based on a multifactorial approach and includes pharmacotherapy targeted against the predominant symptom, behavioural and psychological treatment, dietary alterations, education, reassurance and effective patient-physician relationship. When evaluating for the stress-induced condition in the upper GI tract, the diagnostic testing includes mainly blood tests and gastroscopy to rule out GERD and peptic ulcer disease. The therapy for these conditions is mainly based on the inhibition of gastric acid by proton pump inhibitors and eradication of Helicobacter pylori-infection. Additionally, melatonin an important mediator of brain gut axis has been shown to exhibit important protective effects against stress-induced lesions in the gastrointestinal tract. Finally, probiotics may profoundly affect the brain-gut interactions ("microbiome-gut-brain axis") and attenuate the development of stress-induced disorders in both the upper and lower gastrointestinal tract. Further studies on the brain-gut axis are needed to open new therapeutic avenues in the future.
Topics: Animals; Antidiarrheals; Enteric Nervous System; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; Irritable Bowel Syndrome; Probiotics; Stress, Psychological; Treatment Outcome
PubMed: 22314561
DOI: No ID Found -
Nutrients Nov 2019Autism spectrum disorder (ASD) is a complex behavioral syndrome that is characterized by speech and language disorders, intellectual impairment, learning and motor... (Review)
Review
Autism spectrum disorder (ASD) is a complex behavioral syndrome that is characterized by speech and language disorders, intellectual impairment, learning and motor dysfunctions. Several genetic and environmental factors are suspected to affect the ASD phenotype including air pollution, exposure to pesticides, maternal infections, inflammatory conditions, dietary factors or consumption of antibiotics during pregnancy. Many children with ASD shows abnormalities in gastrointestinal (GI) physiology, including increased intestinal permeability, overall microbiota alterations, and gut infection. Moreover, they are "picky eaters" and the existence of specific sensory patterns in ASD patients could represent one of the main aspects in hampering feeding. GI disorders are associated with an altered composition of the gut microbiota. Gut microbiome is able to communicate with brain activities through microbiota-derived signaling molecules, immune mediators, gut hormones as well as vagal and spinal afferent neurons. Since the diet induces changes in the intestinal microbiota and in the production of molecules, such as the SCFA, we wanted to investigate the role that nutritional intervention can have on GI microbiota composition and thus on its influence on behavior, GI symptoms and microbiota composition and report which are the beneficial effect on ASD conditions.
Topics: Autism Spectrum Disorder; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Diet; Fatty Acids, Volatile; Food Preferences; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Neurotransmitter Agents; Nutritional Status; Serotonin
PubMed: 31752095
DOI: 10.3390/nu11112812 -
The Journal of Clinical Investigation Feb 2021The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include... (Review)
Review
The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include motor, secretory, sensory, storage, and excretory functions. Disorders of the nervous system affecting gastrointestinal tract function manifest primarily as abnormalities in motor (rather than secretory) functions. Common gastrointestinal symptoms in neurologic disorders include sialorrhea, dysphagia, gastroparesis, intestinal pseudo-obstruction, constipation, diarrhea, and fecal incontinence. Diseases of the entire neural axis ranging from the cerebral hemispheres to the peripheral autonomic nerves can result in gastrointestinal motility disorders. The most common neurologic diseases affecting gastrointestinal function are stroke, parkinsonism, multiple sclerosis, and diabetic neuropathy. Diagnosis involves identification of the neurologic disease and its distribution, and documentation of segmental gut dysfunction, typically using noninvasive imaging, transit measurements, or intraluminal measurements of pressure activity and coordination of motility. Apart from treatment of the underlying neurologic disease, management focuses on restoration of normal hydration and nutrition and pharmacologic treatment of the gut neuromuscular disorder.
Topics: Diabetic Neuropathies; Enteric Nervous System; Gastrointestinal Diseases; Gastrointestinal Motility; Humans
PubMed: 33586685
DOI: 10.1172/JCI143771 -
Advances in Nutrition (Bethesda, Md.) May 2017Constipation is a common and burdensome gastrointestinal disorder that may result from altered gastrointestinal motility. The effect of probiotics on constipation has... (Review)
Review
Constipation is a common and burdensome gastrointestinal disorder that may result from altered gastrointestinal motility. The effect of probiotics on constipation has been increasingly investigated in both animal and human studies, showing promising results. However, there is still uncertainty regarding the mechanisms of action of probiotics on gut motility and constipation. Several factors are vital to normal gut motility, including immune and nervous system function, bile acid metabolism and mucus secretion, and the gastrointestinal microbiota and fermentation; an imbalance or dysfunction in any of these components may contribute to aberrant gut motility and, consequently, symptoms of constipation. For example, adults with functional constipation have significantly decreased numbers of bifidobacteria (with one study showing a mean difference of 1 log/g) and lactobacilli (mean difference, 1.4 log/g) in stool samples, as well as higher breath methane, compared with control subjects. Modifying the gut luminal environment with certain probiotic strains may affect motility and secretion in the gut and, hence, provide a benefit for patients with constipation. Therefore, this review explores the mechanisms through which probiotics may exert an effect on gut motility and constipation. Nevertheless, the majority of current evidence is derived from animal studies, and therefore, further human studies are needed to determine the mechanisms through specific probiotic strains that might be effective in constipation.
Topics: Animals; Constipation; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Probiotics
PubMed: 28507013
DOI: 10.3945/an.116.014407