title: The digestive tract as the origin of systemic inflammation.
abstract: Failure of gut homeostasis is an important factor in the pathogenesis and progression of systemic inflammation, which can culminate in multiple organ failure and fatality. Pathogenic events in critically ill patients include mesenteric hypoperfusion, dysregulation of gut motility, and failure of the gut barrier with resultant translocation of luminal substrates. This is followed by the exacerbation of local and systemic immune responses. All these events can contribute to pathogenic crosstalk between the gut, circulating cells, and other organs like the liver, pancreas, and lungs. Here we review recent insights into the identity of the cellular and biochemical players from the gut that have key roles in the pathogenic turn of events in these organ systems that derange the systemic inflammatory homeostasis. In particular, we discuss the dangers from within the gastrointestinal tract, including metabolic products from the liver (bile acids), digestive enzymes produced by the pancreas, and inflammatory components of the mesenteric lymph.
authors.affiliation: Department of Pediatric Intensive Care, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands. pdejong@sbpdiscovery.org.|Sanford Burnham Prebys Medical Discovery Institute, 10901 N Torrey Pines Rd, La Jolla, CA, 92037, USA. pdejong@sbpdiscovery.org.
authors.forename: Petrus R
authors.initials: PR
authors.lastname: de Jong
authors.affiliation: Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Hospital General Universitario de Alicante, Alicante, Spain.|Alicante Institute of Health and Biomedical Research (ISABIAL - FISABIO Foundation), Alicante, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: González-Navajas
authors.affiliation: Department of Pediatric Intensive Care, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Nicolaas J G
authors.initials: NJ
authors.lastname: Jansen
mesh_terms: D016824:Antigens, Human Platelet / Q000378:metabolism; D001647:Bile Acids and Salts / Q000009:adverse effects / Q000502:physiology; D005234:Fatty Liver / Q000150:complications; D041981:Gastrointestinal Tract / Q000503:physiopathology*; D006501:Hepatic Encephalopathy / Q000150:complications; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D009102:Multiple Organ Failure / Q000503:physiopathology / Q000517:prevention & control; D010538:Peritonitis / Q000150:complications; D050791:STAT Transcription Factors / Q000493:pharmacokinetics
chemical_list: D016824:Antigens, Human Platelet; D001647:Bile Acids and Salts; D050791:STAT Transcription Factors; C083451:human platelet antigen 1b
keywords: Acute inflammation; Gastrointestinal failure; Gut-liver crosstalk; Pancreatitis