The microbiome and critical illness

Abstract

The central role of the microbiome in critical illness is supported by a half century of experimental and clinical study. The physiological effects of critical illness and the clinical interventions of intensive care substantially alter the microbiome. In turn, the microbiome predicts patients' susceptibility to disease, and manipulation of the microbiome has prevented or modulated critical illness in animal models and clinical trials. This Review surveys the microbial ecology of critically ill patients, presents the facts and unanswered questions surrounding gut-derived sepsis, and explores the radically altered ecosystem of the injured alveolus. The revolution in culture-independent microbiology has provided the tools needed to target the microbiome rationally for the prevention and treatment of critical illness, holding great promise to improve the acute and chronic outcomes of the critically ill.

Figure 1. The altered ecosystem of the critically ill patient

Changes in microbiota depend upon severity of illness rather than physical location and bacterial exposure.

Figure 2. Manipulation of the microbiome and the prevention of critical illness

(A) In diverse models of shock, germ-free mice are protected from the alveolar inflammation and injury seen in acute respiratory distress syndrome. (B) In clinical trials, manipulation of gut microbiota with antibiotics (selective decontamination of the digestive tract) protects against extra-abdominal infections, multiorgan failure, and death.^, Part A was adapted from reference 90 by permission of the American Association of Immunologists.

Figure 3. Alteration of bacterial ecology in injured alveoli

(A) Unlike in the healthy gut, the environment in healthy lungs is nutrient poor for bacteria and the protein content of alveolar lavage fluid is at a minimum. (B) In states of health, bacterial growth in the alveolar space is limited by the local inflammatory response it provokes and by its depletion of available nutrients. In conditions of alveolar injury, such as in ARDS and pneumonia, the alveolar space is flooded with nutrient-rich fluid, which promotes bacterial growth that in turn perpetuates a positive-feedback loop of inflammation, injury, alveolar oedema, and further dysbiosis. BAL=bronchoalveolar lavage. ARDS=acute respiratory distress syndrome. Part B was reproduced from reference 113 by permission of Elsevier.

Figure 4. Catecholamines and disorder in the alveolar bacterial ecosystem

(A) The growth of bacteria, such as Pseudomonas aeruginosa, is promoted in vitro by catecholamines, such as norepinephrine and dopamine. (B) In the human lung microbiome, increased catecholamine concentrations are strongly associated with community collapse and the emergence of one dominant species. (C) In states of critical illness, direct and indirect lung injury provoke alveolar inflammation, which promotes catecholamine production and creates a positive-feedback loop of dysbiosis and inflammation. CFU=colony forming unit. VILI=ventilator-induced lung injury. Part A adapted from reference 51 by permission of American College of Chest Physicians. Part B adapted from reference 50 by permission of American Thoracic Society.