Editors' ChoiceMicrobiome

Lung dysbiosis drives post hematopoietic cell transplantation inflammation

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Science Translational Medicine  04 Jul 2018:
Vol. 10, Issue 448, eaau1973
DOI: 10.1126/scitranslmed.aau1973

Abstract

Changes in the structure and composition of the lung microbiota are associated with pulmonary complications in hematopoietic cell transplantation.

Pulmonary complications are very common among subjects undergoing hematopoietic cell transplantation (HCT) and carry significant morbidity and mortality. Although some of these are due to overt infection with a pathogen, many others are characterized by increased inflammation without an obvious pathogen (as in bronchiolitis obliterans and idiopathic pneumonia syndromes). Some changes in gut microbiota (for example, low diversity and enrichment with enterococci and proteobacteria) have recently been described as associated with pulmonary complications in HCT. However, recent studies of the lung microbiota are teaching us that the lung microbiota is probably a more important determinant of the lung mucosal inflammatory state than the gut is. This may also be true in the inflammatory processes occurring in the lung after HCT.

O'Dwyer et al. recently investigated this issue, using culture-independent methods to study the effects of the lung microbiota on pulmonary inflammation during HCT. Using a preclinical mouse model, the authors observed that experimental HCT altered the composition of the lung microbiota, and this effect was potentiated when mice were also exposed to herpes virus. Importantly, these changes were associated with development of pneumonitis. The authors then extended these observations to a human cohort of 43 patients undergoing HCT whose lower airways were sampled via bronchoscopy. In these subjects, lung dysbiosis signatures were associated with lung dysfunction and alveolar inflammation. For example, lower relative abundance of Firmicutes was associated with higher levels of proinflammatory cytokines, in particular IFN-α2, in the lower airways.

In the new era of studying microbes using omics, the gut microbiota has received the most attention as a major determinant of host immune status that may affect lung diseases, via a gut-lung interaction. However, new insights about the lower airway microbiota have moved us away from the preconception that the lung was sterile and allowed us to discover the magnitude of direct effects that microbes have on the host immune system at the lung mucosa interface. The data presented in this paper provide proof of concept about how an altered lung microbiota can lead to lower airway inflammation and pulmonary complications.

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