The role of the local microbial ecosystem in respiratory health and disease

Abstract

Respiratory tract infections are a major global health concern, accounting for high morbidity and mortality, especially in young children and elderly individuals. Traditionally, highly common bacterial respiratory tract infections, including otitis media and pneumonia, were thought to be caused by a limited number of pathogens including Streptococcus pneumoniae and Haemophilus influenzae. However, these pathogens are also frequently observed commensal residents of the upper respiratory tract (URT) and form-together with harmless commensal bacteria, viruses and fungi-intricate ecological networks, collectively known as the 'microbiome'. Analogous to the gut microbiome, the respiratory microbiome at equilibrium is thought to be beneficial to the host by priming the immune system and providing colonization resistance, while an imbalanced ecosystem might predispose to bacterial overgrowth and development of respiratory infections. We postulate that specific ecological perturbations of the bacterial communities in the URT can occur in response to various lifestyle or environmental effectors, leading to diminished colonization resistance, loss of containment of newly acquired or resident pathogens, preluding bacterial overgrowth, ultimately resulting in local or systemic bacterial infections. Here, we review the current body of literature regarding niche-specific upper respiratory microbiota profiles within human hosts and the changes occurring within these profiles that are associated with respiratory infections.

Keywords: bacterial interaction; colonization resistance; microbiome; pathogenesis; respiratory infections; upper respiratory tract.

Figure 1.

Niche-specific bacterial community structure of the anterior nares, the nasopharynx and the oropharynx (which resembles the oral cavity). Microbial interaction networks associated with these anatomical locations are depicted, with potential driving environmental forces (acidity, oxygen availability and presence of antimicrobial compounds). Coloured circles represent individual bacterial community members, which are interconnected by dotted blue and red lines, respectively, representing positive and negative associations. Microbial community members are colour-coded based on phylum level; Firmicutes: red/brown, Actinobacteria: yellow, Bacteroidetes: green, Proteobacteria: blue and Fusobacteria: purple. S: Streptococcus spp.; Spn: S. pneumoniae; Sv: S. salivarius; Spy: S. pyogenes; Sd: S. dysgalactiae; Sag: S. agalactiae; Sa: S. aureus; V: Veillonella spp.; D: Dolosigranulum spp.; LB: Lactobacillus spp.; CB: Corynebacterium spp.; PB: Propionibacterium spp.; B: Bacteroidetes; P: Prevotella spp.; M: Moraxella spp.; Mc: M. catarrhalis; Hi: H. influenzae; N: Neisseria spp.; L: Leptotrichia spp. and F: Fusobacterium spp.

Figure 2.

Hypothetical model on the relationship between the URT microbiome and pathogenesis of infectious respiratory diseases. This figure shows the potential mechanistic explanations for the influence of the URT microbiome on colonization resistance, reduction of which is presumed to be at the core of the pathogenesis of acute respiratory infections, such as AOM, pharyngitis and tonsillitis. In (a), we show the optimal situation in which keystones species, for example Bacteroidetes members for the oropharynx, are at the base of a diverse ecological system of bacterial interactions. (b) Depicts a situation in which synergistic or antagonistic interspecies interactions modulate microbial composition and biodiversity, consequently regulating colonization resistance. For example, the release of metabolic by-products, such as short chain fatty acids (SCFAs) from fermenting bacteria, results in acidification of the environment and inhibition of growth of acidophobic bacteria, such as S. aureus. Furthermore, production of bactericidal products such as hydrogen peroxide or bacteriocins results in exclusion of certain bacterial species. In (c), we demonstrate that a Proteobacteria-rich microbiome is associated with a low-grade inflammation through activation of Toll-like receptor 4 (TLR-4) by hepta- or hexa-acylated lipopolysaccharide (LPS), which might forego invasion of pathogenic species. This immunostimulatory effect is reduced and even counteracted when the TLR-4 receptor is activated by tetra- and penta-acylated LPS, of members of the phylum Bacteroidetes, such as Prevotella spp. (d) Demonstrates the situation in which viral infection results in exposure of fibrinogen (not shown) through virus-induced epithelial cell damage. Additionally, viral infection, but also the presence of potential pathogenic bacterial species such as H. influenzae results in upregulation of adhesion receptors. Moreover, viral infection reduces epithelial integrity, thus contributing to bacterial translocation. Finally, the presence of influenza virus increases the availability of host-derived sialic acid-rich mucins, resulting in increased pneumococcal replication. For colour-codes of various bacterial community members, see the legend of figure 1. ICAM-1, intercellular adhesion molecule 1; CEACAM-1, carcinoembryonic antigen-related cell adhesion molecule 1; PAF-r, platelet-activating factor receptor; IL, interleukin; TNF, tumour necrosis factor. Δ: change in/of.