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Molecular Psychiatry Apr 2023Irritable bowel syndrome (IBS) is the most prevalent disorder of brain-gut interactions that affects between 5 and 10% of the general population worldwide. The current... (Review)
Review
Irritable bowel syndrome (IBS) is the most prevalent disorder of brain-gut interactions that affects between 5 and 10% of the general population worldwide. The current symptom criteria restrict the diagnosis to recurrent abdominal pain associated with altered bowel habits, but the majority of patients also report non-painful abdominal discomfort, associated psychiatric conditions (anxiety and depression), as well as other visceral and somatic pain-related symptoms. For decades, IBS was considered an intestinal motility disorder, and more recently a gut disorder. However, based on an extensive body of reported information about central, peripheral mechanisms and genetic factors involved in the pathophysiology of IBS symptoms, a comprehensive disease model of brain-gut-microbiome interactions has emerged, which can explain altered bowel habits, chronic abdominal pain, and psychiatric comorbidities. In this review, we will first describe novel insights into several key components of brain-gut microbiome interactions, starting with reported alterations in the gut connectome and enteric nervous system, and a list of distinct functional and structural brain signatures, and comparing them to the proposed brain alterations in anxiety disorders. We will then point out the emerging correlations between the brain networks with the genomic, gastrointestinal, immune, and gut microbiome-related parameters. We will incorporate this new information into a systems-based disease model of IBS. Finally, we will discuss the implications of such a model for the improved understanding of the disorder and the development of more effective treatment approaches in the future.
Topics: Humans; Irritable Bowel Syndrome; Enteric Nervous System; Abdominal Pain; Brain
PubMed: 36732586
DOI: 10.1038/s41380-023-01972-w -
American Journal of Medical Genetics.... Mar 2017The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint...
The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagen-encoding genes, or in genes encoding collagen-modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes. © 2017 Wiley Periodicals, Inc.
Topics: Collagen; Connective Tissue Diseases; Ehlers-Danlos Syndrome; Genetic Heterogeneity; Humans; Mutation; Practice Guidelines as Topic
PubMed: 28306229
DOI: 10.1002/ajmg.c.31552 -
Clinical Gastroenterology and... Jan 2019Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the... (Review)
Review
BACKGROUND & AIMS
Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders.
METHODS
We reviewed the preclinical and clinical literature related to the topic of brain gut microbiome interactions.
RESULTS
Well-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programmed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established.
CONCLUSIONS
Targets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders.
Topics: Biological Factors; Brain; Gastrointestinal Microbiome; Gastrointestinal Tract; Host Microbial Interactions; Humans; Microbiota
PubMed: 30292888
DOI: 10.1016/j.cgh.2018.10.002 -
Internal Medicine Journal Jan 2015Portal hypertension is an important complication of liver disease. As a result of elevated pressures within the portal vein several complications can arise, including... (Review)
Review
Portal hypertension is an important complication of liver disease. As a result of elevated pressures within the portal vein several complications can arise, including the development of oesophageal and gastric varices, ascites, hepatic encephalopathy as well as complications secondary to circulatory dysfunction, such as hepatorenal syndrome, portopulmonary syndrome and hepatopulmonary syndrome. This review outlines the pathogenesis and diagnosis of portal hypertension and outlines the management of these various important clinical sequelae. The management of oesophageal and gastric varices is particularly important, and both the emergency management together with prophylactic management of this condition are described.
Topics: Diagnostic Imaging; Disease Management; Humans; Hypertension, Portal; Portal Vein; Tomography, X-Ray Computed; Ultrasonography, Doppler; Vascular Resistance; Venous Pressure
PubMed: 25230084
DOI: 10.1111/imj.12590 -
Cancers Jul 2020Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are... (Review)
Review
Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are responsible for syndromes that predispose to osteosarcomas including Li Fraumeni syndrome, retinoblastoma syndrome, Werner syndrome, Bloom syndrome or Diamond-Blackfan anemia. is the most frequently altered gene in osteosarcoma. Among other genes mutated in more than 10% of OS cases, c-Myc plays a role in OS development and promotes cell invasion by activating MEK-ERK pathways. Several genomic studies showed frequent alterations in the gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in , , , , , , and genes. Some miRNAs such as miR-21, -34a, -143, -148a, -195a, -199a-3p and -382 regulate the pathogenic activity of MAPK and PI3K/Akt-signaling pathways in osteosarcoma. CD133+ osteosarcoma cells have been shown to exhibit stem-like gene expression and can be tumor-initiating cells and play a role in metastasis and development of drug resistance. Although currently osteosarcoma treatment is based on adriamycin chemoregimens and surgery, there are several potential targeted therapies in development. First of all, activity and safety of cabozantinib in osteosarcoma were studied, as well as sorafenib and pazopanib. Finally, novel bifunctional molecules, of potential imaging and osteosarcoma targeting applications may be used in the future.
PubMed: 32751922
DOI: 10.3390/cancers12082130 -
Acta Dermato-venereologica Apr 2019Skin cancer has become the most common type of cancer worldwide as a result of environmental exposure and medical treatments. A small group of patients are genetically... (Review)
Review
Skin cancer has become the most common type of cancer worldwide as a result of environmental exposure and medical treatments. A small group of patients are genetically predisposed to skin cancer and this article is intended as a diagnostic tool when encountering patients with multiple skin cancer lesions. The disorders are described with clinical characteristics, genetics and management. The most common syndromes associated with basal cell carcinoma are: Gorlin-Goltz syndrome, Rombo syndrome, and Bazex-Dupré-Christol syndrome. Multiple squamous cell carcinomas can be related to: xeroderma pigmentosum, Ferguson-Smith, Muir-Torre syndrome, Mibelli-type porokeratosis, keratitis-ichthyosis-deafness syndrome, Rothmund-Thomson syndrome, Bloom syndrome, and epidermodysplasia verruciformis. Malignant melanoma can be inherited, as in familial atypical multiple mole melanoma syndrome.
Topics: Adolescent; Adult; Biomarkers, Tumor; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Male; Melanoma; Middle Aged; Mutation; Neoplastic Syndromes, Hereditary; Phenotype; Risk Assessment; Risk Factors; Skin; Skin Neoplasms; Treatment Outcome; Young Adult
PubMed: 30653245
DOI: 10.2340/00015555-3123 -
Annals of Clinical Biochemistry May 2019Bile acids have important roles in the regulation of lipid, glucose and energy metabolism. Metabolic diseases linked to obesity, including type 2 diabetes mellitus and... (Review)
Review
Bile acids have important roles in the regulation of lipid, glucose and energy metabolism. Metabolic diseases linked to obesity, including type 2 diabetes mellitus and non-alcoholic fatty liver disease, are associated with dysregulation of bile acid homeostasis. Here, the basic chemistry and regulation of bile acids as well as their metabolic effects will be reviewed. Changes in circulating bile acids associated with obesity and related diseases will be reviewed. Finally, pharmaceutical manipulation of bile acid homeostasis as therapy for metabolic diseases will be outlined.
Topics: Bile Acids and Salts; Humans; Metabolic Syndrome
PubMed: 30453753
DOI: 10.1177/0004563218817798