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Inflammatory Bowel Diseases Nov 2023Several patients with ulcerative colitis (UC) suffer from psychiatric disorders, such as major depressive disorder, anxiety, or bipolar disorder, and show specific...
BACKGROUND
Several patients with ulcerative colitis (UC) suffer from psychiatric disorders, such as major depressive disorder, anxiety, or bipolar disorder, and show specific personality traits. Despite this, there are few data about personality profiles' characterization in UC patients and about correlation of their psychopathological profile with their intestinal microbiota.The aim of our study is to analyze the psychopathological and personality profile of UC patients and correlate it with specific signatures of their gut microbiota.
METHODS
This is a prospective interventional longitudinal cohort study. We enrolled consecutive patients affected by UC attending to the IBD Unit of Center for Digestive Disease of "A. Gemelli" IRCCS Hospital in Rome and a group of healthy subjects, matched for specific characteristics. Each patient was evaluated by a gastroenterologist and a psychiatrist. Moreover, all participants underwent psychological tests and a collection of stool samples.
RESULTS
We recruited 39 UC patients and 37 healthy subjects. Most patients showed high level of alexithymia, anxiety symptoms, depressive symptoms, as well as neuroticism and hypochondria, with obsessive-compulsive features at the behavioral level, which significantly impaired their quality of life and abilities at work. Gut microbiota analysis in UC patients demonstrated an increase in actinobacteria, Proteobacteria and Saccharibacteria (TM7), with a reduction in verrucomicrobia, euryarchaeota and tenericutes.
CONCLUSIONS
Our study confirmed the presence of high levels of psycho-emotional distress in UC patients, alongside alterations of the intestinal microbiota, and highlighted some families and genera of bacteria (Enterobacteriaceae, Streptococcus, Veillonella, Klebsiella, and Clostridiaceae) as potential markers of an altered gut-brain axis in these patients.
Topics: Humans; Colitis, Ulcerative; Gastrointestinal Microbiome; Longitudinal Studies; Depressive Disorder, Major; Prospective Studies; Quality of Life; Bacteria
PubMed: 37280117
DOI: 10.1093/ibd/izad091 -
BMC Medicine Sep 2023Colorectal adenoma (CA), especially high-risk CA (HRCA), is a precancerous lesion with high prevalence and recurrence rate and accounts for about 90% incidence of...
BACKGROUND
Colorectal adenoma (CA), especially high-risk CA (HRCA), is a precancerous lesion with high prevalence and recurrence rate and accounts for about 90% incidence of sporadic colorectal cancer cases worldwide. Currently, recurrent CA can only be treated with repeated invasive polypectomies, while safe and promising pharmaceutical invention strategies are still missing due to the lack of reliable in vitro model for CA-related drug screening.
METHODS
We have established a large-scale patient-derived high-risk colorectal adenoma organoid (HRCA-PDO) biobank containing 37 PDO lines derived from 33 patients and then conducted a series of high-throughput and high-content HRCA drug screening.
RESULTS
We established the primary culture system with the non-WNT3a medium which highly improved the purity while maintained the viability of HRCA-PDOs. We also proved that the HRCA-PDOs replicated the histological features, cellular diversity, genetic mutations, and molecular characteristics of the primary adenomas. Especially, we identified the dysregulated stem genes including LGR5, c-Myc, and OLFM4 as the markers of adenoma, which are well preserved in HRCA-PDOs. Based on the HRCA-PDO biobank, a customized 139 compound library was applied for drug screening. Four drugs including metformin, BMS754807, panobinostat and AT9283 were screened out as potential hits with generally consistent inhibitory efficacy on HRCA-PDOs. As a representative, metformin was discovered to hinder HRCA-PDO growth in vitro and in vivo by restricting the stemness maintenance.
CONCLUSIONS
This study established a promising HRCA-PDO biobank and conducted the first high-throughput and high-content HRCA drug screening in order to shed light on the prevention of colorectal cancer.
Topics: Humans; Biological Specimen Banks; Drug Evaluation, Preclinical; Organoids; Adenoma; Colorectal Neoplasms; Metformin
PubMed: 37667332
DOI: 10.1186/s12916-023-03034-y -
International Journal of Molecular... Feb 2024Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and... (Review)
Review
Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and neuroprotective properties. It exhibits the potential to prevent or slow the progression of various diseases, ranging from malignant tumors and viral infections to neurodegenerative disorders and ischemic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis stand as prominent causes of morbidity and mortality in chronic liver diseases globally. The literature has substantiated CBD's potential therapeutic effects across diverse liver diseases in in vivo and in vitro models. However, the precise mechanism of action remains elusive, and an absence of evidence hinders its translation into clinical practice. This comprehensive review emphasizes the wealth of data linking CBD to liver diseases. Importantly, we delve into a detailed discussion of the receptors through which CBD might exert its effects, including cannabinoid receptors, CB1 and CB2, peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 55 (GPR55), transient receptor potential channels (TRPs), and their intricate connections with liver diseases. In conclusion, we address new questions that warrant further investigation in this evolving field.
Topics: Humans; Cannabidiol; Receptors, Cannabinoid; Cannabis; Digestive System Diseases; Liver Diseases, Alcoholic; Receptor, Cannabinoid, CB1
PubMed: 38397045
DOI: 10.3390/ijms25042370 -
Gut Aug 2023Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of...
BACKGROUND AND AIMS
Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models.
METHODS
Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling.
RESULTS
Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality.
CONCLUSIONS
Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF.
Topics: Humans; Prognosis; Prospective Studies; Methoxyhydroxyphenylglycol; Liver Cirrhosis; Acute-On-Chronic Liver Failure; Inflammation; Metabolomics; Mitochondria
PubMed: 36788015
DOI: 10.1136/gutjnl-2022-328708 -
Arquivos Brasileiros de Cirurgia... 2023Achalasia is an esophageal motility disorder, and myotomy is one of the most used treatment techniques. However, symptom persistence or recurrence occurs in 9 to 20% of... (Review)
Review
BACKGROUND
Achalasia is an esophageal motility disorder, and myotomy is one of the most used treatment techniques. However, symptom persistence or recurrence occurs in 9 to 20% of cases.
AIMS
This study aims to provide a practical approach for managing the recurrence or persistence of achalasia symptoms after myotomy.
METHODS
A critical review was performed to gather evidence for a rational approach for managing the recurrence or persistence of achalasia symptoms after myotomy.
RESULTS
To properly manage an achalasia patient with significant symptoms after myotomy, such as dysphagia, regurgitation, thoracic pain, and weight loss, it is necessary to classify symptoms, stratify severity, perform appropriate tests, and define a treatment strategy. A systematic differential diagnosis workup is essential to cover the main etiologies of symptoms recurrence or persistence after myotomy. Upper digestive endoscopy and dynamic digital radiography are the main tests that can be applied for investigation. The treatment options include endoscopic dilation, peroral endoscopic myotomy, redo surgery, and esophagectomy, and the decision should be based on the patient's individual characteristics.
CONCLUSIONS
A good clinical evaluation and the use of proper tests jointly with a rational assessment, are essential for the management of symptoms recurrence or persistence after achalasia myotomy.
Topics: Humans; Deglutition Disorders; Endoscopy; Esophageal Achalasia; Esophageal Sphincter, Lower; Esophagectomy; Myotomy; Natural Orifice Endoscopic Surgery; Treatment Outcome
PubMed: 38088726
DOI: 10.1590/0102-672020230062e1780 -
Journal of Hepatology Jan 2024Primary sclerosing cholangitis (PSC) was declared one of the biggest unmet needs in hepatology during International Liver Congress 2016 in Berlin. Since then, not much... (Review)
Review
Primary sclerosing cholangitis (PSC) was declared one of the biggest unmet needs in hepatology during International Liver Congress 2016 in Berlin. Since then, not much has changed unfortunately, largely due to the still elusive pathophysiology of the disease. One of the most striking features of PSC is its association with inflammatory bowel disease (IBD), with the majority of patients with PSC being diagnosed with extensive colitis. This review describes the epidemiology of IBD in PSC, its specific phenotype, complications and potential pathophysiological mechanisms connecting the two diseases. Whether PSC is merely an extra-intestinal manifestation of IBD or if PSC and IBD are two distinct diseases that happen to share a common susceptibility that leads to a dual phenotype is debated. Implications for the management of the two diseases together are also discussed. Overall, this review summarises the available data in PSC-IBD and discusses whether PSC and IBD are one or two disease(s).
Topics: Humans; Cholangitis, Sclerosing; Inflammatory Bowel Diseases; Liver; Phenotype
PubMed: 37940453
DOI: 10.1016/j.jhep.2023.09.031 -
Neuroscience Letters Jul 2023Although our understanding of the pathophysiology of inflammatory bowel disease (IBD) is increasing, the expanding body of knowledge does not simplify the equation but...
Although our understanding of the pathophysiology of inflammatory bowel disease (IBD) is increasing, the expanding body of knowledge does not simplify the equation but rather reveals diverse, interconnected, and complex mechanisms in IBD. In addition to immune overactivation, defects in intestinal epithelial barrier (IEB) functioning, dysbiosis, and structural and functional abnormalities of the enteric nervous system are emerging as new elements contributing to the development of IBD. In addition to molecular changes in IBD, enteric glia from patients with Crohn's disease (CD) exhibits the inability to strengthen the IEB; these defects are not observed in patients with ulcerative colitis. In addition, there is a growing body of work describing that enteric glia interacts with not only enterocytes and enteric neurons but also other local cellular neighbours. Thus, because of their functions as connectors and regulators of immune cells, IEB, and microbiota, enteric glia could be the keystone of digestive homeostasis that is lacking in patients with CD.
Topics: Humans; Inflammatory Bowel Diseases; Intestines; Crohn Disease; Neuroglia; Neurons
PubMed: 37257681
DOI: 10.1016/j.neulet.2023.137315 -
The Korean Journal of Gastroenterology... Nov 2023Portal hypertension is a clinical syndrome defined by an increased portal venous pressure. The most frequent cause of portal hypertension is liver cirrhosis, and many of... (Review)
Review
Portal hypertension is a clinical syndrome defined by an increased portal venous pressure. The most frequent cause of portal hypertension is liver cirrhosis, and many of the complications of cirrhosis, such as ascites and gastroesophageal variceal bleeding, are related to portal hypertension. Portal hypertension is a pathological condition caused by the accumulation of blood flow in the portal system. This blood flow retention reduces the effective circulation volume. To compensate for these changes, neurotransmitter hormone changes and metabolic abnormalities occur, which cause complications in organs other than the liver. A hepatic hydrothorax is fluid accumulation in the pleural space resulting from increased portal pressure. Hepatopulmonary syndrome and portopulmonary hypertension are the pulmonary complications in cirrhosis by deforming the vascular structure. Symptoms, such as dyspnea and hypoxia, affect the survival and the quality of life of patients. These lung complications are usually underestimated in the management of cirrhosis. This review briefly introduces the type of lung complications of cirrhosis.
Topics: Humans; Esophageal and Gastric Varices; Hypertension, Pulmonary; Quality of Life; Gastrointestinal Hemorrhage; Liver Cirrhosis; Hepatopulmonary Syndrome; Hypertension, Portal
PubMed: 37997217
DOI: 10.4166/kjg.2023.123 -
Lakartidningen Sep 2023Gastroesophageal reflux disease (GERD) is characterized by regurgitation of gastric juices into the esophagus. This has an erosive effect on the mucosa with accompanying... (Review)
Review
Gastroesophageal reflux disease (GERD) is characterized by regurgitation of gastric juices into the esophagus. This has an erosive effect on the mucosa with accompanying symptoms, such as heartburn, acid regurgitation and positional-/exertion--induced chest pain. The associated inflammation in the multi-layered squamous epithelium of the esophagus (esophagitis) can usually be seen macroscopically at gastroscopy and is always possible to demonstrate microscopically as well-characterized changes. GERD is abundant in the adult population in the Western world, and the incidence appears to be increasing. Serious manifestations of GERD include the appearance of esophageal injury (esophagitis) and columnar lined esophagus (Barrett's esophagus) and, in rare cases, peptic stricture. The glandular-transformed (metaplastic) mucosa carries its clinical significance by constituting the basis for continued cell transformation (development of dysplasia), which eventually might lead to esophageal adenocarcinoma (EAC). EAC is an aggressive form of cancer whose incidence continues to increase in particular in the Western part of the world. In this article the potential mechanisms for the development of the metaplastic glandular epithelium and its progression to dysplasia and cancer is reviewed. In addition, recommendations are given on how important signals about future risks can be captured and managed and how these risks can be minimized and preferably prevented.
Topics: Adult; Humans; Barrett Esophagus; Esophageal Neoplasms; Esophagitis; Gastroesophageal Reflux; Chest Pain
PubMed: 37746770
DOI: No ID Found -
Clinical Gastroenterology and... Feb 2024Irritable bowel syndrome (IBS) is a common, debilitating disorder characterized by abdominal pain and disordered bowel habits. Current pharmacologic treatments often... (Review)
Review
BACKGROUND & AIMS
Irritable bowel syndrome (IBS) is a common, debilitating disorder characterized by abdominal pain and disordered bowel habits. Current pharmacologic treatments often provide incomplete symptom relief and may be poorly tolerated. Furthermore, alleviation of gastrointestinal symptoms does not always translate into improved quality of life for IBS patients. Current treatment guidelines recommend brain-gut behavior therapy (BGBT) in conjunction with other IBS therapies, and, in randomized controlled trials, BGBT has been shown to improve symptoms, patient satisfaction, functioning, and quality of life. Access to BGBT is limited by lack of adequately trained gastrointestinal psychologists, patient time constraints, and cost. Furthermore, clinician knowledge that BGBT is specific, and different from psychotherapy approaches for common mental health disorders, may limit referrals even where available. This review provides an overview of the pathophysiology of IBS, disease burden, unmet therapeutic needs, evidence base of novel digital therapeutics for IBS, and guidance on the introduction and appropriateness of these interventions for patients.
METHODS
We searched the literature for available published data relating to the use of novel digital therapeutics to provide cognitive behavioral therapy and gut-directed hypnotherapy in the treatment of irritable bowel syndrome.
RESULTS
Clinical trial data support the development and utility of digital therapeutics designed to deliver self-guided cognitive behavioral therapy and hypnotherapy for the treatment of IBS.
CONCLUSIONS
BGBTs are effective, guideline-recommended treatments for IBS. Digital therapeutic devices offer accessible, cost-effective treatment options for delivery of adjunctive BGBT for the treatment of IBS. The decision to recommend digital BGBTs should be guided by careful patient assessment that includes mental health screening and risk assessment.
Topics: Humans; Irritable Bowel Syndrome; Quality of Life; Cognitive Behavioral Therapy; Behavior Therapy; Treatment Outcome
PubMed: 37743035
DOI: 10.1016/j.cgh.2023.09.013