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.
Numerous studies, dating back nearly a century, have demonstrated that microaspiration is common in healthy, asymptomatic subjects 2-5, and knowledge of the bacterial content of inhaled air is as ...old as germ theory itself 6. Since the first culture-independent report of the healthy lung microbiome 7, more than 30 published studies using molecular techniques for bacterial identification have found evidence of bacteria in the lower airways. ...the community membership of the lung microbiome is altered in disease states.
Summary Culture-independent microbiological techniques have shown a previously unappreciated complexity to the bacterial microbiome of the respiratory tract that forces reconsideration of the ...interactions between host, bacteria, and the pathogenesis of exacerbations of chronic lung disease. The composition of the lung microbiome is determined by microbial immigration, elimination, and relative growth rates of its members. All these factors change dramatically in chronic lung disease and further during exacerbations. Exacerbations lack the features of bacterial infections, including increased bacterial burden and decreased diversity of microbial communities. We propose that exacerbations are occasions of respiratory tract dysbiosis—a disorder of the respiratory tract microbial ecosystem with negative effects on host biology. Respiratory tract dysbiosis provokes a dysregulated host immune response, which in turn alters growth conditions for microbes in airways, promoting further dysbiosis and perpetuating a cycle of inflammation and disordered microbiota. Differences in the composition of baseline respiratory tract microbiota might help to explain the so-called frequent-exacerbator phenotype observed in several disease states, and might provide novel targets for therapeutic intervention.
The Microbiome and the Respiratory Tract Dickson, Robert P; Erb-Downward, John R; Martinez, Fernando J ...
Annual review of physiology,
01/2016, Letnik:
78, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Although the notion that "the normal lung is free from bacteria" remains common in textbooks, it is virtually always stated without citation or argument. The lungs are constantly exposed to diverse ...communities of microbes from the oropharynx and other sources, and over the past decade, novel culture-independent techniques of microbial identification have revealed that the lungs, previously considered sterile in health, harbor diverse communities of microbes. In this review, we describe the topography and population dynamics of the respiratory tract, both in health and as altered by acute and chronic lung disease. We provide a survey of current techniques of sampling, sequencing, and analysis of respiratory microbiota and review technical challenges and controversies in the field. We review and synthesize what is known about lung microbiota in various diseases and identify key lessons learned across disease states.
The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The ...microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships.
Racial Bias in Pulse Oximetry Measurement Sjoding, Michael W; Dickson, Robert P; Iwashyna, Theodore J ...
New England journal of medicine/The New England journal of medicine,
12/2020, Letnik:
383, Številka:
25
Journal Article
Although culture-independent techniques have refuted lung sterility in health, controversy about contamination during bronchoscope passage through the upper respiratory tract (URT) has impeded ...research progress. We sought to establish whether bronchoscopic sampling accurately reflects the lung microbiome in health and to distinguish between two proposed routes of authentic microbial immigration, (i) dispersion along contiguous respiratory mucosa and (ii) subclinical microaspiration. During bronchoscopy of eight adult volunteers without lung disease, we performed seven protected specimen brushings (PSB) and bilateral bronchoalveolar lavages (BALs) per subject. We amplified, sequenced, and analyzed the bacterial 16S rRNA gene V4 regions by using the Illumina MiSeq platform. Rigorous attention was paid to eliminate potential sources of error or contamination, including a randomized processing order and the inclusion and analysis of exhaustive procedural and sequencing control specimens. Indices of mouth-lung immigration (mouth-lung community similarity, bacterial burden, and community richness) were all significantly greater in airway and alveolar specimens than in bronchoscope contamination control specimens, indicating minimal evidence of pharyngeal contamination. Ecological indices of mouth-lung immigration peaked at or near the carina, as predicted for a primary immigration route of microaspiration. Bacterial burden, diversity, and mouth-lung similarity were greater in BAL than PSB samples, reflecting differences in the sampled surface areas. (This study has been registered at ClinicalTrials.gov under registration no. NCT02392182.)
This study defines the bacterial topography of the healthy human respiratory tract and provides ecological evidence that bacteria enter the lungs in health primarily by microaspiration, with potential contribution in some subjects by direct dispersal along contiguous mucosa. By demonstrating that contamination contributes negligibly to microbial communities in bronchoscopically acquired specimens, we validate the use of bronchoscopy to investigate the lung microbiome.
Pseudomonas fluorescens is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it at low levels in the indigenous ...microbiota of various body sites. With recent advances in comparative genomics, many isolates originally identified as the "species" P. fluorescens are now being reclassified as novel Pseudomonas species within the P. fluorescens "species complex." Although most widely studied for its role in the soil and the rhizosphere, P. fluorescens possesses a number of functional traits that provide it with the capability to grow and thrive in mammalian hosts. While significantly less virulent than P. aeruginosa, P. fluorescens can cause bacteremia in humans, with most reported cases being attributable either to transfusion of contaminated blood products or to use of contaminated equipment associated with intravenous infusions. Although not suspected of being an etiologic agent of pulmonary disease, there are a number of reports identifying it in respiratory samples. There is also an intriguing association between P. fluorescens and human disease, in that approximately 50% of Crohn's disease patients develop serum antibodies to P. fluorescens. Altogether, these reports are beginning to highlight a far more common, intriguing, and potentially complex association between humans and P. fluorescens during health and disease.
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