The gut microbiota is pivotal for maintaining health through beneficial symbiotic interaction with the host supporting the homeostasis of the gastrointestinal tract but also of the majority of extraintestinal organs. Alterations in the gut microbiome have been linked to the pathogenesis of various diseases, including cancer, which remains a leading cause of mortality worldwide. The colonisation or

Background Early detection of colorectal cancer (CRC) is crucial for improving the survival rates of patients. Objective We aimed to develop a novel strategy for early CRC detection using the fragmentomic features of circulating cell-free mitochondrial DNA (ccf-mtDNA). Design Here, a total of 1147 participants, including 478 healthy controls (HCs), 112 patients with advanced adenomas (AAs) and 557

Objective Ampullary neoplastic lesions can be resected by endoscopic papillectomy (EP) or transduodenal surgical ampullectomy (TSA) while pancreaticoduodenectomy is reserved for more advanced lesions. We present the largest retrospective comparative study analysing EP and TSA. Design Of all patients in the database, lesions with prior interventions, benign histology advanced malignancy (T2 and more)

Background Transmembrane 6 superfamily member 2 (TM6SF2) has a protective role against metabolic dysfunction-associated steatotic liver disease (MASLD). Objective We aim to investigate the mechanistic role and therapeutic potential of hepatic TM6SF2 in MASLD-related hepatocellular carcinoma (HCC). Design Hepatocyte-specific Tm6sf2 knockout ( Tm6sf2 ∆hep) mice were fed with high-fat/high-cholesterol

Background One in three children with Crohn’s disease develop perianal fistula complications (PFCs), among the most disturbing and difficult-to-treat disease-related complications. Retrospective evidence suggests PFCs may be preventable. Objective We aimed to determine if early antitumour necrosis factor-alpha (anti-TNF⍺) therapy prevents PFC development in a well-characterised prospective cohort of

Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, carrying a greater risk of developing cirrhosis and its complications. For decades, pegylated interferon alpha (PegIFN-α) has represented the only therapeutic option, with limited virological response rates and poor tolerability. In 2020, the European Medicines Agency approved bulevirtide (BLV) at 2 mg/day, an entry inhibitor of

Immune checkpoint inhibitors (ICI) have led to breakthrough improvements in the management of malignancy including hepatocellular (HCC) and biliary tract cancer, improving decades-old standards of care and increasing patient survival. In both liver tumour types, which commonly arise in the context of liver inflammation and underlying functional impairment, the lack of validated predictors of response

Perturbation of mRNA splicing is commonly observed in human cancers and plays a role in various aspects of cancer hallmarks. Understanding the mechanisms and functions of alternative splicing (AS) not only enables us to explore the complex regulatory network involved in tumour initiation and progression but also reveals potential for RNA-based cancer treatment strategies. This review provides a comprehensive

Hepatocellular carcinoma (HCC) is often diagnosed at the unresectable stage with limited treatment options.1 Immunotherapy with immune checkpoint blockade (ICB) has been shown to provide significant survival benefit for HCC patients with advanced disease. Two combination therapies of anti-PD-L1 plus anti-VEGF or anti-PD1 plus anti-CTLA4 represent the current first-line treatments for unresectable HCC

Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated condition characterised by eosinophilic infiltration of the oesophagus, leading to significant morbidity due to oesophageal dysfunction. The pathogenic course of EoE begins with tissue injury, marked by the intricate interplay of oesophageal barrier dysfunction and T helper 2-mediated inflammation. In response to tissue damage, a subsequent

Background Over a century ago, Virchow proposed that cancer represents a chronically inflamed, poorly healing wound. Normal wound healing is represented by a transitory phase of inflammation, followed by a pro-resolution phase, with prostaglandin (PGE2/PGD2)-induced ‘lipid class switching’ producing inflammation-quenching lipoxins (LXA4, LXB4). Objective We explored if lipid dysregulation in colorectal

Background Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive malignancy with a dismal prognosis, and gaps remain in understanding the determinants influencing disease outcomes. Objective To characterise the gut microbiota feature and identify potential probiotics that could ameliorate the development of NKTCL. Design This cross-sectional study employed shotgun metagenomic sequencing to

The close association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is an important starting point to understand PSC but may also be of interest to understand IBD. In Gut , Bedtke et al present an extensive set of experiments designed to test the impact of sclerosing cholangitis on IBD.1 The results show that both genetic and induced sclerosing cholangitis lead to

The colonisation and assembly of the neonatal microbiota is essential for the development and maturation of the immune system, and the early life from birth to 2 years of age is regarded as a crucial window period. Abnormal microbial colonisation and reduced gut microbiota diversity during this period are linked to the subsequent development of immune-mediated diseases. Dysbiosis of intestinal microbiota

Several studies have highlighted the significance of targeting fat mass and obesity-associated protein (FTO) in gastrointestinal cancers including hepatocellular carcinoma (HCC) .1 The recent study from the group of Irene Oi-Lin Ng presented in Gut by Chen et al 2 introduces new insights into the molecular dynamics of HCC, focusing on the pivotal role of FTO in the disease’s pathophysiology. Functioning

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

Despite significant advances in biologic and small molecule treatments and the emergence of combination therapies to treat inflammatory bowel diseases (IBD) a large unmet need remains to control intestinal inflammation. New approaches targeting several pathways simultaneously with a favorable safety profile and agents that trigger anti-inflammatory pathways to drive durable resolution of inflammation

Background Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. Objective To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management

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

Background Colonic motility in constipation can be assessed non-invasively using MRI. Objective To compare MRI with high-resolution colonic manometry (HRCM) for predicting treatment response. Design Part 1: 44 healthy volunteers (HVs), 43 patients with irritable bowel syndrome with constipation (IBS-C) and 37 with functional constipation (FC) completed stool diaries and questionnaires and underwent

Objective The specific breast milk-derived metabolites that mediate host–microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation. Design We enrolled 250 mother–infant pairs and collected 978 longitudinal faecal samples from infants from birth to 6 months of age, along with 243 maternal faecal samples for metagenomics. Concurrently

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 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 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

Objective Fat mass and obesity-associated protein (FTO), an eraser of N 6-methyadenosine (m6A), plays oncogenic roles in various cancers. However, its role in hepatocellular carcinoma (HCC) is unclear. Furthermore, small extracellular vesicles (sEVs, or exosomes) are critical mediators of tumourigenesis and metastasis, but the relationship between FTO-mediated m6A modification and sEVs in HCC is unknown

Objective Patients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased numbers of circulating and hepatic neutrophils. Design In this study, we performed tandem mass tag (TMT) proteomics to analyse proteins in the faeces of controls (n=19), patients with

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

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

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of liver injuries, ranging from hepatic steatosis, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and the gut microbial community

Artificial intelligence (AI) holds significant potential for enhancing quality of gastrointestinal (GI) endoscopy, but the adoption of AI in clinical practice is hampered by the lack of rigorous standardisation and development methodology ensuring generalisability. The aim of the Quality Assessment of pre-clinical AI studies in Diagnostic Endoscopy (QUAIDE) Explanation and Checklist was to develop

A gentleman in his early 40s with a background of schizophrenia on clozapine presented with a 2-month history of rectal bleeding, diarrhoea, weight loss, a microcytic anaemia and a quantitative faecal immunochemical test (qFIT) result >400 µg Hb/g. Colonoscopy demonstrated multiple large polypoid lesions in the rectum and in the sigmoid colon; the sigmoid was unable to be passed by the colonoscope

With great interest, we read the article by Konings et al ,1 in which the authors conducted a combined case–control and cohort study and found that dysphagia, gastroparesis, irritable bowel syndrome (IBS) without diarrhoea and constipation specifically predict subsequent newly onset idiopathic Parkinson’s disease (PD) through comparing patients with PD with matched negative controls and patients with

We thank the authors for their interest in our report on endoscopic ultrasound-guided gallbladder drainage (EUS-GBD).1 Management of gallbladder disease is not within the sole domain of gastroenterologists. It includes surgeons and interventional radiologists. When guidelines are developed without multidisciplinary consensus, problems can occur as reported in our series.2 The distinction between never-surgery

Recently, we were intrigued by a recent study by Fong and colleagues,1 in which they found that Lactobacillus gallinarum could reduce regulatory T-cell (Treg) infiltration and enhance CD8+ T-cell effector function, thus improving anti-PD1 efficacy in patients with colorectal cancer, which was confirmed in mouse models. Interestingly, Lactobacillus was observed to be related to smoke exposure, with

With great interest, we carefully read the article by Lei et al .1 The authors introduced a novel ‘family index-case method’ to efficiently screen for and eradicate Helicobacter pylori ( H. pylori ) infections by reaching out to the family members of individuals who tested positive. However, the article predominantly focused on detailing the methodology of the ‘family index-case method’, rather than

We read with interest the population-based cohort studies by Abrahami et al on proton pump inhibitors (PPI) and the risk of gastric and colon cancers.1 2 PPI are used at all levels of healthcare and across different subspecialties for various indications.3 4 A recent systematic review on the global trends and practices of PPI recognised 28 million PPI users from 23 countries, suggesting that 23.4%

A recent population-based cohort study found an association between proton pump inhibitor (PPI) prescription and risk of inflammatory bowel disease which they attributed to protopathic bias (ie, the drug was prescribed in response to initial disease symptoms) rather than a causal effect of PPI usage.1 In a following Mendelian randomisation (MR) study, An et al selected genetic variants associated with

In an article published in April 2022 in Gut , the authors introduced an enhancer-based classification system known as EpiC, which facilitated the epigenomic categorisation of colorectal cancer (CRC).1 Following this, a novel approach was presented in a recent issue of Nature Genetics , dated 13 February, by Malla et al . This study diverges from traditional gene-centric analysis typically seen in

We read with great interest the meta’omic study by Kong et al 1 which reported on metagenomic sequencing of faecal samples to discover microbiome-derived biomarkers for colorectal cancer (CRC). Faecal immunochemical test (FIT) samples provide consistent microbiome profiling based on 16S rRNA gene (ie, amplicon-based) sequencing when compared with immediately frozen samples from whole stool2 and are

We have read with great interest and excitement the article by Wang et al ,1 in which the authors demonstrated that pancreatic overexpression of the human trypsin inhibitor SPINK1 (serine protease inhibitor Kazal type 1, also known as pancreatic secretory trypsin inhibitor) via an adeno-associated viral (AAV) vector significantly improved pancreatitis severity and outcomes in preclinical mouse models

Recently, the article by Konings et al systematically articulated the association between gastrointestinal syndrome and Parkinson’s disease (PD),1 which found that appendectomy reduced the risk of PD. According to Braak’s hypothesis2 that α-synuclein aggregation may begin in the gut and be transmitted to the brain via vagus nerve, appendectomy could remove α-synuclein and vagus nerve terminals in the

López-Gil JC, García-Silva S, Ruiz-Cañas L, et al. The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem …

Cholangiocarcinoma (CCA) is a highly aggressive adenocarcinoma of the biliary tract system with unsatisfactory therapeutic options.1 Standard frontline treatment for unresectable or metastatic CCA consisting of cisplatin and gemcitabine combined with checkpoint inhibitors targeting programmed cell death ligand 1 or programmed cell death 1 offers objective response rates of less than 30% and a median

We are delighted that Fritzsche et al have expressed an interest in our randomised trial investigating the effects of endoluminal radiofrequency ablation (RFA) on survival and stent patency in cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) patients.1 2 We fully agree that plastic stents are likely to exhibit shorter patency in patients with CCA. The low patency in our small subgroup

We would like to thank Dunne et al 1 for their interest in our work.2 Their main concerns are that the rates of liver-related events (LREs) including progression to ascites were similar in both the groups in spite of lower mortality and oesophageal variceal bleed (OVB) in the combination arm as compared with the other arms. Second, the rates of OVBs and the bleed-related mortality were higher in the

Background Common genetic variation at 11q23.1 is associated with colorectal cancer (CRC) risk, exerting local expression quantitative trait locus (cis-eQTL) effects on POU2AF2 , COLCA1 and POU2AF3 genes. However, complex linkage disequilibrium and correlated expression has hindered elucidation of the mechanisms by which genetic variants impart underlying CRC risk. Objective Undertake an interdisciplinary

Clinically effective pharmacological treatment(s) for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) represent a largely unmet need in medicine. Since glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been licensed for the treatment of type 2 diabetes mellitus and obesity, they were one of the

We read with interest the recently published randomised controlled trial (RCT) ‘SPHINX’,1 addressing the role of endoscopic sphincterotomy (ES) with fully covered s metal stent (FCSEMS) placement in preventing post-ERCP pancreatitis (PEP). Although this is the largest RCT on the topic, several concerns warrant discussion. Published data report variable rates of PEP after SEMS ranging from 0% to 26

Background It is unknown which maintenance therapy is the most effective option for patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous steroids. Methods We conducted a multicentre, parallel-group, open-label randomised controlled trial among 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids

Background A spatially resolved, niche-level analysis of tumour microenvironments (TME) can provide insights into cellular interactions and their functional impacts in gastric cancers (GC). Objective Our goal was to translate the spatial organisation of GC ecosystems into a functional landscape of cellular interactions involving malignant, stromal and immune cells. Design We performed spatial transcriptomics

Objective Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks closely associated with hepatic overproduction of potentially neurotoxic heme precursors. Design We replicated AIP in non-human primates (NHPs) through selective

Background Gastric intestinal metaplasia (IM) is a precancerous stage spanning a morphological spectrum that is poorly represented by human cell line models. Objective We aim to establish and characterise human IM cell models to better understand IM progression along the cancer spectrum. Design A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids

We read with interest the Rome Consensus paper on faecal microbiota transplantation (FMT) in IBD (a refractory disease with intermittent flare-ups and remissions of intestinal inflammation) by Lopetuso et al .1 It highlights modest efficacies of FMT in treating IBD and adverse event risks caused by bacteria transplantation, according to data from clinical trials.1 Hence, further refinement of FMT is

Background Aberrant Wnt pathway activation is a key driver of colorectal cancer (CRC) and is essential to sustain tumour growth and progression. Although the downstream protein-coding target genes of the Wnt cascade are well known, the long non-coding transcriptome has not yet been fully resolved. Objective In this study, we aim to comprehensively reveal the Wnt-regulated long non-coding transcriptome

Background There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett’s oesophagus (BE). Objective To develop and test a blood-based assay for EAC and BE. Design Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia ( EMERALD ) was a large, international, multicentre biomarker cohort study involving 792 patient

We read with great interest the article by Henniger et al 1 about reducing scope 3 carbon emissions in endoscopy and would like to discuss several points. First, we commend the study’s transparency, as manufacturers provided detailed information about their fabrication and delivery processes. This collaboration exemplifies our shared goal of environmental protection. Furthermore, this is the first

Background Peritoneal metastasis is the most common metastasis pattern of gastric cancer. Patients with gastric cancer peritoneal metastasis (GCPM) have a poor prognosis and respond poorly to conventional treatments. Recently, immune checkpoint blockade (ICB) has demonstrated favourable efficacy in the treatment of GCPM. Stratification of best responders and elucidation of resistance mechanisms of

Many patients with IBD report persisting symptoms, despite resolution of the inflammatory process. Although by definition, a diagnosis of IBS cannot be made, the prevalence of ‘IBS in IBD’ surpasses the rate of IBS in the global population by fivefold. Because IBS-like symptoms are associated with a decreased quality of life and increased healthcare utilisation in IBD, diagnosis and treatment are necessary

Surgical removal is recommended for gastrointestinal stromal tumours (GISTs) larger than 3 cm due to their potential for malignancy but limited wedge resection is not possible in the proximal stomach. Endoscopic removal of larger lesions has been technically limited in complex anatomical regions such as cardia. We report two cases of large proximal (cardia/fundus) GIST tumours (51 and 60 mm) which

Chronic hepatitis B virus (HBV) infection remains a significant global health burden, affecting over 250 million people worldwide who are at risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Currently available nucleos(t)ide analogues (NAs) are effective in controlling viraemia; however, functional cure, defined as loss of hepatitis B surface antigen (HBsAg), is rare and difficult