Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease

Javier Cabrera-Perez; Vladimir P Badovinac; Thomas S Griffith

doi:10.1177/1535370216669610

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Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease

Journal article

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Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease

Javier Cabrera-Perez, Vladimir P Badovinac and Thomas S Griffith

Experimental biology and medicine (Maywood, N.J.), Vol.242(2), pp.127-139

01/2017

DOI: 10.1177/1535370216669610

PMCID: PMC5167116

PMID: 27633573

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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.

Bacteria - immunology

CD4-Positive T-Lymphocytes - immunology

Critical Illness

Gastrointestinal Microbiome - immunology

Germ Theory of Disease

Humans

Intestinal Mucosa - immunology

Intestinal Mucosa - microbiology

Intestinal Mucosa - physiopathology

Sepsis - immunology

Sepsis - microbiology

Sepsis - pathology

Details

Title: Subtitle: Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease
Creators: Javier Cabrera-Perez - University of Minnesota
Vladimir P Badovinac - University of Minnesota
Thomas S Griffith - University of Minnesota
Resource Type: Journal article
Publication Details: Experimental biology and medicine (Maywood, N.J.), Vol.242(2), pp.127-139
DOI: 10.1177/1535370216669610
PMID: 27633573
PMCID: PMC5167116
NLM abbreviation: Exp Biol Med (Maywood)
ISSN: 1535-3702
eISSN: 1535-3699
Grant note: R01 GM113961 / NIGMS NIH HHS I01 BX001324 / BLRD VA R01 AI114543 / NIAID NIH HHS R21 AI119160 / NIAID NIH HHS T32 AI007313 / NIAID NIH HHS R01 GM115462 / NIGMS NIH HHS
Language: English
Date published: 01/2017
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984180921502771

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