The pulmonary microbiome: challenges of a new paradigm

Abstract

The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.

Figure 1. Sequence of events leading to the recognition of the microbiome at a given site. OTU: operational taxonomic unit.

Figure 2. Determinants of the lung microbiome and the intestine-lung axis. The composition of the human microbiota is determined by the association of environmental factors, the host immune response, and genetic characteristics. The intestine microbiota, which is incomparably greater in size than the lung microbiota, can influence the lower respiratory tract both directly, through microaspiration, and indirectly, through modulation of the immune response as a result of the production of bacterial metabolites and their interaction with the host inflammatory cells. Inhalation of external agents is also a pathway to lung colonization and will depend, as will intestinal tract colonization, on local factors, such as oxygen tension, tissue pH, blood perfusion, nutrient concentration, proper mucociliary transport, and disruption of the lung architecture.

Figure 3. Determinants of the microbiome of the respiratory system: microbial immigration, elimination, and proliferation. In healthy individuals, the microbiome is determined primarily by immigration and elimination. In severe lung disease, local growth conditions are determinants of the composition of the microbiome.

Figure 4. Microbiota interface and interaction with local immunity. Members of the microbiota, in association with environmental non-viable particulate antigens, are continuously sampled by the mucosa and processed by dendritic cells and macrophages, with subsequent formation of memory or activation of T and B effector cells. Therefore, various commensal microorganisms influence the innate immunity and the adaptive immunity.