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Chapter 7 : Lung Microbiota and Its Impact on the Mucosal Immune Phenotype

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Abstract:

In 2007, the Human Microbiome Project (HMP) was added to the National Institutes of Health (NIH) Roadmap for Medical Research, and since then, over $200 million has been invested in the exploration of the human microbiome. Several sites on the human body, including the nares, oral cavity, skin, gastrointestinal tract, and urogenital tract, have been studied by the HMP ( ). The gastrointestinal tract remains the most thoroughly investigated organ-microbiome interaction studied thus far, and its role in shaping the host immune response is rapidly becoming defined within the context of inflammatory response ( ). Observations have noted associations of specific microbes and the gut microbiome in obesity ( ), coronary artery disease ( ), colitis ( ), type 2 diabetes ( ), and inflammatory bowel disease ( ). While the nares and oral cavity were included as locations to be studied for the HMP, the lower airway respiratory system was not included as a location of interest. The microbial community of the oropharynx had been well described even before the advances of next-generation sequencing and multiplexed data ( ). Microbiome approaches to the upper and lower respiratory systems created a deluge of associations between host and microbes in health and disease ( ). Over the past few years, our understanding of the airway microbiome has shifted, upending the old adage of the lungs being a sterile field ( ) to a new paradigm of a continuous organ system with a rich and vibrant mucosal surface that embodies complex interactions between the microbiome and its host that can propagate or resist disease ( ). Moreover, little is known regarding how the respiratory microbiome interacts with the host immune response. While multiple research projects have focused on the effects of the gut microbiota on the immune response of the gastrointestinal mucosa ( ), few papers have focused on the effects of the lower airway microbiota on the respiratory mucosa that it inhabits ( ).

Citation: Wu B, Segal L. 2018. Lung Microbiota and Its Impact on the Mucosal Immune Phenotype, p 161-186. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0005-2016
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Figure 1

Conceptual model: signal-to-noise ratio. (A) Healthy gastrointestinal microbiome, where there is an organ of healthy biomass and background “noise” or signal amplified by background (e.g., background microbiota present in the colonoscope) that does not represent the gut microbiome. This background microbiome is overwhelmed by the large biomass present the sample. (B) Healthy lung microbiome, where there is relatively low biomass and background signals tend to overwhelm the lung microbiome signal. (C) Diseased gastrointestinal microbiome, where the pathogenic signal (dysbiosis) will eventually overcome the high underlying biomass. The pathogenic signal will overpower the background microbiome and be apparent given the high amount of biomass present in the gut. (D) Diseased lung microbiome. Unlike the diseased gut microbiome, the pathogenic signal may be confounded by the background noise and may not be apparent until sufficient progression of disease supports the altered dysbiosis.

Citation: Wu B, Segal L. 2018. Lung Microbiota and Its Impact on the Mucosal Immune Phenotype, p 161-186. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0005-2016
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Image of Figure 2
Figure 2

Host-microbiota interaction in the lung. This schema represents the normal lung microbiome and its dysbiosis. In this model, enrichment with background taxa (represented as blue bacteria) in pneumotype occurs in a lung with preserved mucociliary clearance of microorganisms and minimal inflammatory signals within the lung. In the presence of enrichment of the lower airway microbiome with oral taxa (represented as red bacteria) in pneumotype, there will be upregulation of the Th17 inflammatory phenotype and recruitment of neutrophils and lymphocytes. PMN, polymorphonuclear leukocyte.

Citation: Wu B, Segal L. 2018. Lung Microbiota and Its Impact on the Mucosal Immune Phenotype, p 161-186. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0005-2016
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