The Human Respiratory System and its Microbiome at a Glimpse

Abstract

The recent COVID-19 pandemic promoted efforts to better understand the organization of the respiratory microbiome and its evolution from birth to adulthood and how it interacts with external pathogens and the host immune system. This review aims to deepen understanding of the essential physiological functions of the resident microbiome of the respiratory system on human health and diseases. First, the general characteristics of the normal microbiota in the different anatomical sites of the airways have been reported in relation to some factors such as the effect of age, diet and others on its composition and stability. Second, we analyze in detail the functions and composition and the correct functionality of the microbiome in the light of current knowledge. Several studies suggest the importance of preserving the micro-ecosystem of commensal, symbiotic and pathogenic microbes of the respiratory system, and, more recently, its relationship with the intestinal microbiome, and how it also leads to the maintenance of human health, has become better understood.

Keywords: SARS-CoV-2; asthma; clinical microbiology; dysbiosis; human microbiome; immune modulation; respiratory diseases; respiratory microbiome; translational research.

Figure 1

Main bacteria genera and microbiome species of an adult in the upper respiratory tract.

Figure 2

Bidirectional hypothesis that the intestinal microbiota can modulate the immunological activity of the lung: lipopolysaccharides (LPSs) are able to bind to the Toll-Like Receptor (TLR) present on the intestinal mucosa causing the activation of dendritic cells that favor the activation of various T cells (T-reg, T-h17, Th-1, CD4); subsequently, there is the acquisition of horning receptors (CCR6, CCR9, CCR4, a4b7) and migration to the lung through the circulatory lymphatic flow (CCR4/6Treg, CCR4/6Th17, CCR4/6Th1, CCR4/6CD4 +). It also activates (IL-18, INF-y, TNF-a, TGF-b, IL-4, IL-1), which will pass into the circulation (INF-y, TNF-a, IL-6). The nuclear factor kappa-light chain enhancer of (NFkB) activates IL-6, IL-10 and the production of IgA and IgG plasma cell b cells and the migration of IgG to the lung. In the lung, we have the increase in CCL17, CCL20 and the presence of CCR4/6, CD4 +, CCR4/6 and Th17. The migration of bacterial metabolites (e.g., short-chain fatty acids (SCFAs) to the lung through the bloodstream results in the down-regulation of pattern recognition receptors (PRR) with a consequent reduction in the production of inflammatory cytokines (IL-1, IL-12, IL-18), tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ) and granulocyte–macrophage colony stimulating factor (GM-CSF). In turn, the lungs send inflammation mediators and lymphocytes to the gut in case of disease.

Figure 3

The evolution of the upper respiratory tract microbiome during human life and risk of respiratory tract diseases.

Figure 4

Dysbiosis related to some lung diseases. The relative abundance in Proteobacteria is associated with the increased severity of chronic obstructive pulmonary disease (COPD).