title: Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease.
abstract: Sepsis is a poorly understood syndrome of systemic inflammation responsible for hundreds of thousands of deaths every year. The integrity of the gut epithelium and competence of adaptive immune responses are notoriously compromised during sepsis, and the prevalent assumption in the scientific and medical community is that intestinal commensals have a detrimental role in the systemic inflammation and susceptibility to nosocomial infections seen in critically ill, septic patients. However, breakthroughs in the last decade provide strong credence to the idea that our mucosal microbiome plays an essential role in adaptive immunity, where a human host and its prokaryotic colonists seem to exist in a carefully negotiated armistice with compromises and benefits that go both ways. In this review, we re-examine the notion that intestinal contents are the driving force of critical illness. An overview of the interaction between the microbiome and the immune system is provided, with a special focus on the impact of commensals in priming and the careful balance between normal intestinal flora and pathogenic organisms residing in the gut microbiome. Based on the data in hand, we hypothesize that sepsis induces imbalances in microbial populations residing in the gut, along with compromises in epithelial integrity. As a result, normal antigen sampling becomes impaired, and proliferative cues are intermixed with inhibitory signals. This situates the microbiome, the gut, and its complex immune network of cells and bacteria, at the center of aberrant immune responses during and after sepsis.
authors.affiliation: 1 Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA.|2 Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Cabrera-Perez
authors.affiliation: 3 Department of Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.|4 Interdisciplinary Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Badovinac
authors.affiliation: 1 Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota Medical School, Minneapolis, MN 55455, USA.|5 Department of Urology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.|6 Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.|7 Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.|8 Minneapolis VA Health Care System, Minneapolis, MN 55417, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Griffith
mesh_terms: D001419:Bacteria / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016638:Critical Illness; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D060755:Germ Theory of Disease; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology; D018805:Sepsis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology
keywords: Sepsis; T cell; apoptosis; gut microbiome; immune suppression; infection