Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype

Abstract

Microaspiration is a common phenomenon in healthy subjects, but its frequency is increased in chronic inflammatory airway diseases, and its role in inflammatory and immune phenotypes is unclear. We have previously demonstrated that acellular bronchoalveolar lavage samples from half of the healthy people examined are enriched with oral taxa (here called pneumotypeSPT) and this finding is associated with increased numbers of lymphocytes and neutrophils in bronchoalveolar lavage. Here, we have characterized the inflammatory phenotype using a multi-omic approach. By evaluating both upper airway and acellular bronchoalveolar lavage samples from 49 subjects from three cohorts without known pulmonary disease, we observed that pneumotypeSPT was associated with a distinct metabolic profile, enhanced expression of inflammatory cytokines, a pro-inflammatory phenotype characterized by elevated Th-17 lymphocytes and, conversely, a blunted alveolar macrophage TLR4 response. The cellular immune responses observed in the lower airways of humans with pneumotypeSPT indicate a role for the aspiration-derived microbiota in regulating the basal inflammatory status at the pulmonary mucosal surface.

The evaluation of different treatment protocols for combined injury-induced lung injury in rabbits

“…In the air space, an alveloar macrophage secretes cytokines, IL-8 and TNF-α, which act locally to stimulate chemotaxis and activate neutrophis. [25] Our research also shows that IL-8 and TNF-α levels were significantly affected at 24 h post injury in the 1:3 fluid resuscitation group compared with those in the 1:1 fluid resuscitation group (Figure 5c, d). Collectively, these findings suggest that fluid resuscitation significantly attenuates lung injury in rabbit.…”

The respiratory tract microbiome and lung inflammation: a two-way street

“…46 Prevotella -high and -low community profiles have been noted in healthy subjects, 14,30 with the Prevotella- high profile being associated with enhanced “subclinical” lung inflammation, that is notable for enhanced expression of inflammatory cytokines and elevated Th-17 lymphocytes. 30,52 However, association studies do not determine the direction of causality and this data would be very consistent with a model where subclinical airway inflammation leads to higher levels of micro-aspirated Prevotella . In support of this model is the observation in cystic fibrosis patients that colonization with P. aeruginosa , a pro-inflammatory bacteria, significantly increased the likelihood that Prevotella will be present.…”

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis

“…It is possible that the microbiomes may change depending on the grade of fibrosis and honeycomb change. Previous studies have shown that patients with some respiratory past history have different microbiomes than those of healthy volunteers [27]. Furthermore, antibiotics, antacids, inhaled corticosteroids and nutritious food, which can cause microbial changes, should be considered.…”