Background The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity. Objective To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues. Design Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism

The role of the human microbiome in GI disease is an area of significant clinical and academic interest. The microbiome may well influence a number of GI diseases ranging from cancer,1 2 to IBD,3 4 to liver disease.5 6 One of the current challenges faced by microbiome researchers is the variance in terminology, methodological approaches and lack of consistency regarding outcomes. This is an issue that

With great interest, we read the article by Lou et al ,1 who reported deviated gut microbiota in children with autism spectrum disorders (ASD). Recently, increasing studies have revealed abnormalities in extraneural tissues, particularly the gastrointestinal (GI) tract.2 Besides, the important role of lipids in the gut-brain axis of ASD is highlighted by their involvement in neurodevelopmental processes

We would like to offer some critical observations regarding the recent article published on the environmental impact of single-use (SU) versus reusable (RU) gastroscopes.1 The study provides essential insights into the growing concerns about the environmental effects of medical procedures, but we believe there are certain areas that require further clarification and contextual analysis. Specifically

Background While p53 mutations occur early in Barrett’s oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear. Objective This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury. Design We used a BE mouse model (L2-IL1β)

Background Enterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and HEV infection are lacking. Objective This study aimed to establish HAV and HEV infections in multiple small animals by intravenously injecting lipid nanoparticle (LNP)-encapsulated full-length

The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition

Background The potency of T cell-mediated responses is a determinant of immunotherapy effectiveness in treating malignancies; however, the clinical efficacy of T-cell therapies has been limited in hepatocellular carcinoma (HCC) owing to the extensive immunosuppressive microenvironment. Objective Here, we aimed to investigate the key genes contributing to immune escape in HCC and raise a new therapeutic

Background and aims The efficacy of colorectal endoscopic mucosal resection (EMR) is limited by recurrence and the necessity for conservative surveillance. Margin thermal ablation (MTA) after EMR has reduced the incidence of recurrence at the first surveillance colonoscopy at 6 months (SC1). Whether this effect is durable to second surveillance colonoscopy (SC2) is unknown. We evaluated long-term surveillance

Background The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined. Objective We hypothesised that the deconvolution of spatial immune network architectures could identify

We extend our congratulations to Tevethia et al for their recently published ‘CAVARLY trial’, which suggests the combination of variceal band ligation (VBL) and carvedilol is superior to VBL or carvedilol alone in the reduction of the first episode of oesophageal variceal bleeding (OVB) in patients with high-risk varices.1 This is the first primary prophylaxis randomised control trial to examine combination

Background Oncogenic ‘hotspot’ mutations of KRAS and GNAS are two major driver alterations in intraductal papillary mucinous neoplasms (IPMNs), which are bona fide precursors to pancreatic ductal adenocarcinoma. We previously reported that pancreas-specific Kras G12D and Gnas R201C co-expression in p48Cre; KrasLSL-G12D; Rosa26LSL-rtTA; Tg (TetO-GnasR201C) mice ( ‘Kras;Gnas ’ mice) caused development

Alcohol-associated hepatitis (AH) is the acute deterioration of alcohol-related liver disease (ArLD) with rapid onset or worsening of jaundice, which, in severe cases, may transition to acute-on-chronic liver failure (ACLF) with extremely high short-term mortality, increasing with the number and severity of hepatic and extra-hepatic organ dysfunction. Systemic inflammation is a hallmark, driving acute

We read with great interest and would like to commend the informative paper by Dinis–Ribeiro et al on a world-unified approach to the management of gastric intestinal metaplasia (GIM).1 A crucial issue of this approach is to identify subjects with high-risk GIM. The authors suggest that this should involve performing nontargeted biopsies according to mapping protocol even when endoscopy does not suggest

International guidelines recommend that primary prophylaxis of varices in patients with cirrhosis be either non-selective beta-blockers (NSBBs) or variceal band ligation (VBL). These recommendations are based on studies that include both compensated and decompensated patients. Notably, the European Association for the Study of the Liver 2018 guidelines recognise a gap in the efficacy of NSBB therapy

I read with pleasure the paper by Zhou et al 1 analysing the long-term clinical outcomes and changes in liver elastography associated with statin usage in patients with metabolic-associated steatotic liver disease (MASLD). This is a population-based study of 7988 patients selected from a total of 17 849 MASLD patients seen in 16 centres in Europe, America and Asia and who had also transient elastography

Recently, Gut published a review of guidelines for the management of gastric intestinal metaplasia (GIM) with the goal of promoting harmonisation of the guidelines regarding indications for endoscopic screening for gastric cancer and GIM detection/staging, metrics for high-quality endoscopy and non-endoscopic interventions for gastric cancer prevention in patients with GIM.1 GIM is not a disease per

We read with great interest the study by O’Sullivan et al ,1 examining the technical and procedural outcomes of Cold Endoscopic Mucosal Resection (C-EMR) versus Hot EMR (H-EMR). We congratulate the authors for conducting this important research, which adds valuable information to the body of knowledge guiding our choice of the optimal treatment modality for large, benign colorectal polyps. However

TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain receptor 3 (DR3), are members of the TNF and TNFR superfamilies, respectively, with recognised roles in regulating innate and adaptive immune responses; additional existence of a decoy receptor, DcR3, indicates a tightly regulated cytokine system. The significance of TL1A:DR3 signalling in the pathogenesis of inflammatory bowel disease

Background and aims RNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression. Methods We prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside

Recently, we were intrigued by a recent study by Montironi et al ,1 in which they discovered that an inflamed subclass in hepatocellular carcinoma (HCC) patients is associated with a response to immunotherapy. The authors used a 20-gene signature to distinguish these patients and further found different immune infiltration between inflamed and non-inflamed class at the bulk level. We commend the authors

Background Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified. Objective We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA. Design We evaluated the expression of PRMT5, its functional

We have read with great interest the study by Wang et al 1 in which the authors evaluated the utility of the AlphaMissense prediction programme2 (https://alphamissense.hegelab.org) in the classification of missense CPA1 variants with respect to pathogenicity in chronic pancreatitis. While the AI-driven prediction performed relatively well, the authors highlighted potential shortcomings that can limit

Background Tumourigenesis in right-sided and left-sided colons demonstrated distinct features. Objective We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis. Design Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal

Infection with the hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide. With an estimated number of 20 million infections and 3.3 million symptomatic cases, accounting for 3.3% of viral hepatitis-related deaths annually, HEV poses a major public health threat.1 2 Transmission of HEV occurs mainly by the faecal-oral route in low-income and middle-income countries due to poor

Inflammatory bowel diseases (IBD) comprise a spectrum of chronic intestinal inflammatory diseases, mainly ulcerative colitis (UC) and Crohn’s disease (CD), with an increasing incidence worldwide.1 2 Scientific efforts and technological advances led to a profound understanding of IBD pathophysiology, helping to recognise the complex nature and heterogeneity of the IBD spectrum. In recent years, IBD

Barrier healing represents a novel therapeutic target in ulcerative colitis (UC), although its assessment remains challenging and lacks standardisation. This exploratory study evaluates the ability of ultra-high magnification endocytoscopy to guide tissue sampling and drive automated quantification of tight junction (TJ) proteins to assess intestinal barrier integrity and predict major adverse outcomes

Objective During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with

Objective Mutations in presenilin genes are the major cause of Alzheimer’s disease. However, little is known about their expression and function in the gut. In this study, we identify the presenilins Psen1 and Psen2 as key molecules that maintain intestinal homoeostasis. Design Human inflammatory bowel disease (IBD) and control samples were analysed for Psen1 expression. Newly generated intestinal

Objective To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2’FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota

Objective Gut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in the general population, the relationship with overall survival in specific diseases has not been extensively studied. In the current study, we present results from an in-depth analysis

Objective Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. Design We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and

Background Surveillance colonoscopy after polyp removal is recommended to prevent subsequent colorectal cancer (CRC). It is known that advanced adenomas have a substantially higher risk than non-advanced ones, but optimal intervals for surveillance remain unclear. Design We prospectively followed 156 699 participants who had undergone a colonoscopy from 2007 to 2017 in a large integrated healthcare

Objective Highly malignant pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant immunosuppressive and fibrotic tumour microenvironment (TME). Future therapeutic attempts will therefore demand the targeting of tumours and stromal compartments in order to be effective. Here we investigate whether dual specificity and tyrosine phosphorylation-regulated kinase 1B (DYRK1B) fulfil these

Objectives In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. Design All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was

Objective Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. KRAS mutations are among the most abundant genetic alterations in iCCA associated with poor clinical outcome and treatment response. Recent findings indicate that Poly(ADP-ribose)polymerase1 (PARP-1) is implicated in KRAS -driven cancers, but its exact role in cholangiocarcinogenesis

Objective Hepatitis B surface antigen (HBsAg) loss is the optimal outcome for patients with chronic hepatitis B (CHB) but this rarely occurs with currently approved therapies. We aimed to develop and validate a prognostic model for HBsAg loss on treatment using longitudinal data from a large, prospectively followed, nationwide cohort. Design CHB patients receiving nucleos(t)ide analogues as antiviral

Objective Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring

Mounting evidence underscores the pivotal role of the intestinal barrier and its convoluted network with diet and intestinal microbiome in the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CRC). Moreover, the bidirectional association of the intestinal barrier with the liver and brain, known as the gut-brain axis, plays a crucial role in developing complications

Acute severe ulcerative colitis (ASUC), characterised by bloody diarrhoea and systemic inflammation, is associated with a significant risk of colectomy and a small risk of mortality. The landmark trial of cortisone in 1955 was pivotal for two reasons: first, for establishing the efficacy of a drug that remains a first-line therapy today and, second, for producing the first set of disease severity criteria

We were delighted to read the article by Jarosova et al , which presents the results of a randomised controlled trial investigating the efficacy of endobiliary radiofrequency ablation (eRFA).1 The authors should be commended for conducting this large trial not only in pancreatic cancer but also, much rarer, perihilar cholangiocarcinoma (pCCA) patients. Endobiliary RFA uses high frequency current to

We would like to thank Wang et al for their insights and comments on our recently published manuscript ‘Definition of age-dependent reference values for the diameter of the common bile duct and pancreatic duct on MRCP: a population-based, cross-sectional cohort study’.1 2 We beg to differ: previously, body mass index (BMI) has been proposed as having a moderate influence on duct diameters (r<0.3).3

We congratulate Djinbachian et al on their recent publication that addressed the utility of hybrid argon plasma coagulation (hAPC) to mitigate recurrence after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs).1 In a 3-centre study, involving 391 patients (427 LNPCPs), they reported a lower residual or recurrent adenoma rate (RRA of 0.9%) with combined margin and

We read with interest the article by Luxenburger and Thimme, summarising current knowledge about hepatic sequelae in the context of SARS-CoV-2 infection.1 As acute liver injury is observed in one-third of the patients with hospitalised COVID-192 3 and chronic liver disease is associated with higher mortality rates,4 a detailed understanding of hepatic susceptibility and dysfunction in the context of

We read with interest the recent paper by Bredenoord et al ,1 in which the authors performed a subgroup analysis of a phase 3 study of dupilumab 300 mg once a week (LIBERTY EoE TREET) showing that dupilumab was effective and well tolerated in patients with eosinophilic oesophagitis (EoE) regardless of prior topical corticosteroids (TCs) use or inadequate response, intolerance and/or contraindication

Recent papers in Gut have highlighted the importance of the genetic makeup and the influence of the gut microbiome on the amount of lactose in the gut in lactose-intolerant individuals.1 2 Here, we present biochemical data strongly suggesting that heterozygous carriers of certain lactase gene ( LCT ) variants could also be lactose-intolerant. It is widely known that lactose malabsorption in adult-type

We recently reported in Gut that the microbiome is unequivocally implicated in early gestational diabetes mellitus (GDM) aetiology, starting in the first trimester (T1),1 and other groups have shown continued microbiota dysbiosis in women with GDM in second trimester (T2) and third trimester (T3).2 In continuation of our T1 research, we now have data showing that dietary interventions, the preferred

We read with great interest the article by Lee et al 1 evaluating the risk of progression from chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) to high-grade dysplasia (HGD) or gastric adenocarcinoma (GA), according to the Operative Link on Gastric Intestinal Metaplasia (OLGIM) staging system. Patients with OLGIM III–IV had a substantially increased risk of HGD/GA, with a median time

We welcome the excellent discussion from Mandarino et al regarding whether thermal ablation of resection base is warranted after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps.1 2 We agree with many of the points raised by the authors. Indeed, a perfect resection technique as evidenced by Mandarino et al is likely to reduce the need for base ablation; however, such perfect

Some years ago a symposium about non-invasive diagnostics attended by engineers and gastroenterologists was opened by the chairman with the following comment about his experience of colonoscopy: ‘you doctors call it discomfort, we patients call it pain’. As recognised by the Newcastle Endoprem, there are other elements which contribute to the apparent dichotomous views of patients, who regard colonoscopy

Alonso-Nocelo M, Ruiz-Cañas L, Sancho P, et al . Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma. Gut 2023;72:345-59. The …

A 46-year-old male patient was referred to our tertiary care hospital with multiple therapy refractory severely active ulcerative colitis (diagnosis since approximately 1 year). He was previously treated with infliximab, prednisolone, vedolizumab, filgotinib and mercaptopurine. There was no significant medical history. Six weeks prior to admission at our ward, our patient was diagnosed with Kaposi

Objective Sphincter of Oddi disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurisation at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD. Design Prospective cohort conducted at 14 US centres with 12 months follow-up. Patients undergoing first-time endoscopic

Background Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated. Objective We aimed to assess the global, regional and national burden of gastrointestinal cancers. Designs Data on oesophagus, gastric, colorectal, liver, pancreas and biliary tract cancers were extracted from the Global Burden of

Objective To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Design This population-based cohort study was conducted using a nationwide healthcare claims database

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the end-stage of chronic liver diseases, including metabolic-associated steatohepatitis (MASH), an advanced form of metabolic dysfunction-associated steatotic liver disease. The incidence of MASH-driven HCC is expected to continue rising throughout the world due to its association with the obesity and type 2 diabetes epidemic

The absolute number of annual cases of gastric cancer in Europe is rising. The Council of the European Union has recommended implementation of gastric cancer screening for countries or regions with a high gastric cancer incidence and death rates. However, as of 2024 no organised gastric cancer screening programme has been launched in Europe. There are several ways to decrease gastric cancer burden

We have read with interest the recent paper by Gyawali et al .1 The authors deserve commendation for their efforts in developing an update to the Lyon Consensus 2.0, a substantial undertaking involving expert contributors worldwide to establish criteria for diagnosing gastro-esophageal reflux disease (GERD). They have introduced new normal values for existing parameters, such as mean nocturnal baseline

Objective Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal cancers, marked by its lethality and limited treatment options, including the utilisation of checkpoint blockade (ICB) immunotherapy. Epigenetic dysregulation is a defining feature of tumourigenesis that is implicated in immune surveillance, but remains elusive in PDAC. Design To identify the factors that modulate immune

We read with great interest the systematic review by Honap et al 1 and commend the authors for highlighting the elevated risk of colectomy in patients with acute severe UC. While there is ample knowledge about colectomy as a last resort treatment in UC,2 little is known about the colectomy risk in microscopic colitis (MC).3–6 As the incidence of MC has been on the rise over the past decades,7 with