Airway and Lung Microbiome Importance in the Critically Ill

Abstract and Introduction

Abstract

During critical illness, there are a multitude of forces such as antibiotic use, mechanical ventilation, diet changes and inflammatory responses that could bring the microbiome out of balance. This so-called dysbiosis of the microbiome seems to be involved in immunological responses and may influence outcomes even in individuals who are not as vulnerable as a critically ill ICU population. It is therefore probable that dysbiosis of the microbiome is a consequence of critical illness and may, subsequently, shape an inadequate response to these circumstances.

Bronchoscopic studies have revealed that the carina represents the densest site of bacterial DNA along healthy airways, with a tapering density with further bifurcations. This likely reflects the influence of micro-aspiration as the primary route of microbial immigration in healthy adults. Though bacterial DNA density grows extremely sparse at smaller airways, bacterial signal is still consistently detectable in bronchoalveolar lavage fluid, likely reflecting the fact that lavage via a wedged bronchoscope samples an enormous surface area of small airways and alveoli. The dogma of lung sterility also violated numerous observations that long predated culture-independent microbiology.

The body's resident microbial consortia (gut and/or respiratory microbiota) affect normal host inflammatory and immune response mechanisms. Disruptions in these host-pathogen interactions have been associated with infection and altered innate immunity.

In this narrative review, we will focus on the rationale and current evidence for a pathogenic role of the lung microbiome in the exacerbation of complications of critical illness, such as acute respiratory distress syndrome and ventilator-associated pneumonia.

Introduction

The normal microbiota is the ecological communities of commensal, symbiotic and pathogenic microorganisms whilst the microbiome comprises all of the genetic material within a microbiota (the entire collection of microorganisms in a specific niche, such as the human gut). This can also be referred to as the metagenome of the microbiota.^[1,2] Approximately 100 billion microorganisms are found in the body due to recent discoveries in molecular analysis such as next-generation sequencing (NGS) and whole metagenome shotgun sequencing (WMGS); there is an increasing body of evidence pointing towards the dysbiosis that is often defined as an 'imbalance' in the microbial community that is associated with disease.^[3–5]

A microbiome is shaped by multiple factors including the resident flora of the animate or inanimate vicinity and the external forces that modulate this flora.^[6] It becomes a changeable reflection of diversity, and so its study can provide valuable insights into the factors that drive that diversity.^[7] Just as the study of global climate or the roots of language requires input from around the world, so the interpretation of the microbiome of an individual or a group of patients needs comprehensive comparative data to generate insight.^[8,9] The variability of the host microbiome—either in an individual patient over time in response to the pressures of illness^[10] or in a geographically localized population in response to environmental—can yield important insight into factors that can be manipulated to improve clinical outcomes. Such factors include risk of infection, emergence of resistance, spread from the environment, host susceptibility and even the resilience of the health care system.^[11]

Authors and Disclosures

Ignacio Martin-Loeches^1–3* , Robert Dickson^4–6, Antoni Torres⁷, Håkan Hanberger^8,9, Jeffrey Lipman^10,11, Massimo Antonelli^12,13, Gennaro de Pascale^12,13, Fernando Bozza¹⁴, Jean Louis Vincent¹⁵, Srinivas Murthy¹⁶, Michael Bauer¹⁷, John Marshall¹⁸, Catia Cilloniz⁷ and Lieuwe D. Bos¹⁹

¹Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St James Hospital, Dublin 8., Ireland. ²Department of Respiratory Medicine, Hospital Clinic, IDIBAPS, CIBERes, Barcelona, Spain. ³Trinity College, Dublin, Ireland. ⁴Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, USA. ⁵Department of Microbiology and Immunology, University of Michigan, Ann Arbor, USA. ⁶Michigan Center for Integrative Research in Critical Care, Ann Arbor, MI, USA. ⁷Deparment of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB) - SGR 911- Ciber de Enfermedades Respiratorias (Ciberes), Barcelona, Spain. ⁸Department of Infectious Diseases, Linköping University, Linköping, Sweden. ⁹Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. ¹⁰The University of Queensland, Brisbane, Australia. ¹¹Scientific Consultant, Nimes University Hospital, University of Montpellier, Nimes, France. ¹²Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. ¹³Università Cattolica del Sacro Cuore, Rome, Italy. ¹⁴National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil. ¹⁵Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. ¹⁶University of British Columbia, Vancouver, BC V6H 3V4, Canada. ¹⁷Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. ¹⁸The Keenan Research Centre for Biomedical Science, The Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. ¹⁹Department of Respiratory Medicine, Infection and Immunity, Amsterdam University Medical Center, AMC, Amsterdam, The Netherlands.

Authors' contributions
IML has contributed to the conception of the manuscript. RD, AT, HH, JL, MA, GdP, FB, JLV, SM, MB, JM, CC and LB drafted different sections of the manuscript. The authors read and approved the final manuscript.

Competing interests
No COIs to declare.