Cholangiocytes Modulate CD100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation.

Background & Aims: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms.

Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment.

Objective: Primary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer.

enterotoxins tilimycin and tilivalline have distinct host DNA-damaging and microtubule-stabilizing activities.

Establishing causal links between bacterial metabolites and human intestinal disease is a significant challenge. This study reveals the molecular basis of antibiotic-associated hemorrhagic colitis (AAHC) caused by intestinal resident Colitogenic strains produce the nonribosomal peptides tilivalline and tilimycin. Here, we verify that these enterotoxins are present in the human intestine during active colitis and determine their concentrations in a murine disease model.

GPR35 promotes glycolysis, proliferation, and oncogenic signaling by engaging with the sodium potassium pump.

The sodium potassium pump (Na/K-ATPase) ensures the electrochemical gradient of a cell through an energy-dependent process that consumes about one-third of regenerated ATP. We report that the G protein-coupled receptor GPR35 interacted with the α chain of Na/K-ATPase and promotes its ion transport and Src signaling activity in a ligand-independent manner. Deletion of Gpr35 increased baseline Ca to maximal levels and reduced Src activation and overall metabolic activity in macrophages and intestinal epithelial cells (IECs).

Causes of hematochezia and hemorrhagic antibiotic-associated colitis in children and adolescents.

Diseases causing hematochezia range from benign to potentially life-threatening. Systematic pediatric data on the causes of hematochezia are scarce. We studied the underlying causes and long-term outcome of hematochezia in children.

The Toxin-Producing Pathobiont Klebsiella oxytoca Is Not Associated with Flares of Inflammatory Bowel Diseases.

Background: Alterations in the intestinal microbiota are thought to be involved in the pathogenesis of inflammatory bowel diseases (IBD). Klebsiella oxytoca is an intestinal pathobiont that can produce a cytotoxin (tillivaline).

Aim: We aimed to elucidate the pathogenetic relevance of toxin-producing K.

Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis.

Antibiotic therapy disrupts the human intestinal microbiota. In some patients rapid overgrowth of the enteric bacterium Klebsiella oxytoca results in antibiotic-associated hemorrhagic colitis (AAHC). We isolated and identified a toxin produced by K.

Genotypes of Klebsiella oxytoca isolates from patients with nosocomial pneumonia are distinct from those of isolates from patients with antibiotic-associated hemorrhagic colitis.

Klebsiella oxytoca acts as a pathobiont in the dysbiotic human intestinal microbiota, causing antibiotic-associated hemorrhagic colitis (AAHC), but it also infects other organs, resulting in pneumonia and urinary tract and skin infections. The virulence of K. oxytoca is still poorly understood.