Gut

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No abstract text is available yet for this article.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies. DESIGN: We used the KPC mouse model ( LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre ) and primary tumour cell lines to investigate putative CSC populations...

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OBJECTIVE: Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear. DESIGN: We established hepatocyte-specific Sqle transgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce MASH-HCC. SQLE function was also determined in orthotopic and humanised mice...

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, faecal proteome and endocannabinoid (eCB) system. RESULTS: 2'FL supplementation reduced HFD-induced obesity and glucose intolerance...

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury...

OBJECTIVE: The remodelling of gut mycobiome (ie, fungi) during pregnancy and its potential influence on host metabolism and pregnancy health remains largely unexplored. Here, we aim to examine the characteristics of gut fungi in pregnant women, and reveal the associations between gut mycobiome, host metabolome and pregnancy health. DESIGN: Based on a prospective birth cohort in central China (2017 to 2020): Tongji-Huaxi-Shuangliu Birth Cohort, we included 4800 participants who had available ITS2 sequencing data, dietary information and clinical records during their pregnancy...

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OBJECTIVE: Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention. DESIGN: We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings were validated through large-scale histological assays, digital spatial profiler multiplexed immunofluorescence (GeoMx), etc...

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Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines...

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OBJECTIVE: This national analysis aimed to calculate the diagnostic yield from gastroscopy for common symptoms, guiding improved resource utilisation. DESIGN: A cross-sectional study was conducted of diagnostic gastroscopies between 1 March 2019 and 29 February 2020 using the UK National Endoscopy Database. Mixed-effect logistic regression models were used, incorporating random (endoscopist) and fixed (symptoms, age and sex) effects on two dependent variables (endoscopic cancer; Barrett's oesophagus (BO) diagnosis)...

OBJECTIVE: Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models and clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within the liver. Our aim was to characterise the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment...

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 epithelium-specific Psen1-deficient, Psen2-deficient and inducible Psen1/Psen2 double-deficient mice were used to dissect the functional role of presenilins in intestinal homoeostasis...

BACKGROUND AND AIMS: Oesinophilic oesophagitis (EoE) is characterised by symptoms of oesophageal dysfunction and oesinophil tissue infiltration. The EoE Diagnostic Panel (EDP) can distinguish between active and non-active EoE using a set of 77 genes. Recently, the existence of distinct EoE variants featuring symptoms similar to EoE, such as oesophageal dysfunction but lacking eosinophil infiltration, had been determined. METHODS: We used oesophageal biopsies from patients with histologically active (n=10) and non-active EoE (n=9) as well as from healthy oesophageal controls (n=5) participating in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) and analysed the gene expression profile in these biopsies by total RNA-sequencing (RNA-seq)...

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OBJECTIVE: The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding of its biological relevance is limited. Here, we investigated the functional role of the axon guidance cue SEMA3A in supporting PDAC progression. DESIGN: We integrated bulk and single-cell transcriptomic datasets of human PDAC with in situ hybridisation analyses of patients' tissues to evaluate SEMA3A expression in molecular subtypes of PDAC...

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