Therapeutic Targeting of the Respiratory Microbiome

Chotirmall, Sanjay H.; Bogaert, Debby; Chalmers, James D.; Cox, Michael J.; Hansbro, Philip M.; Huang, Yvonne J.; Molyneaux, Philip L.; O’Dwyer, David N.; Pragman, Alexa A.; Rogers, Geraint B.; Dickson, Robert P.

doi:10.1164/rccm.202112-2704pp

Cited by 41 publications

(35 citation statements)

References 73 publications

(115 reference statements)

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“…Bacteriophage therapy has similarly been trialled, although its use is still in its infancy 94 . Other studies have employed both inhaled and systemic antibiotics to modulate the respiratory microbiota but results are mixed across various pulmonary diseases 95 .…”

Section: Discussionmentioning

confidence: 99%

The dynamic lung microbiome in health and disease

2022

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New methods and technologies within the field of lung biology are beginning to shed new light into the microbial world of the respiratory tract. Long considered to be a sterile environment, it is now clear that the human lungs are frequently exposed to live microbes and their by-products. The nature of the lung microbiome is quite distinct from other microbial communities inhabiting our bodies such as those in the gut. Notably, the microbiome of the lung exhibits a low biomass and is dominated by dynamic fluxes of microbial immigration and clearance, resulting in a bacterial burden and microbiome composition that is fluid in nature rather than fixed. As our understanding of the microbial ecology of the lung improves, it is becoming increasingly apparent that certain disease states can disrupt the microbial–host interface and ultimately affect disease pathogenesis. In this Review, we provide an overview of lower airway microbial dynamics in health and disease and discuss future work that is required to uncover novel therapeutic targets to improve lung health.

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Section: Discussionmentioning

confidence: 99%

The dynamic lung microbiome in health and disease

2022

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“…Once we have a deeper understanding of the relevant cellular and molecular mechanisms, new clinical approaches (e.g., pulmonary probiotics, drugs) can be complemented during the treatment of invasive MV, thus maintaining a benign balance of pulmonary microbiota diversity while further exploring how to regulate pulmonary microbiota diversity for a more scientific and efficient clinical management of the therapeutic process of pathogenic diseases [ 84 ]. Some conceptual therapeutic directions include (1) inhalable pulmonary probiotics to maintain a healthy lung microbiota, (2) inhalable drugs specifically/primarily targeting microinhalation of stomach- or mouth-specific microorganisms during invasive stroke, (3) inhalable inflammatory modulators to reduce O2 toxicity or VILI and (4) rational invasive MV procedures to reduce exogenous or endogenous fluid retention and thereby alleviating local O2 concentration perturbations.…”

Section: Discussionmentioning

confidence: 99%

Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota

Liu

Sun

et al. 2022

Crit Care

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Pulmonary microbial diversity may be influenced by biotic or abiotic conditions (e.g., disease, smoking, invasive mechanical ventilation (MV), etc.). Specially, invasive MV may trigger structural and physiological changes in both tissue and microbiota of lung, due to gastric and oral microaspiration, altered body posture, high O2 inhalation-induced O2 toxicity in hypoxemic patients, impaired airway clearance and ventilator-induced lung injury (VILI), which in turn reduce the diversity of the pulmonary microbiota and may ultimately lead to poor prognosis. Furthermore, changes in (local) O2 concentration can reduce the diversity of the pulmonary microbiota by affecting the local immune microenvironment of lung. In conclusion, systematic literature studies have found that invasive MV reduces pulmonary microbiota diversity, and future rational regulation of pulmonary microbiota diversity by existing or novel clinical tools (e.g., lung probiotics, drugs) may improve the prognosis of invasive MV treatment and lead to more effective treatment of lung diseases with precision.

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“…In healthy conditions, it is believed that bacteria in the lungs are at low biomass largely reflecting the upper respiratory tract, whereas changes in regional growth conditions, such as nutrients, oxygen, and inflammation, may drive the expansion of bacteria and the onset of pathological conditions ( 5 , 44 , 45 ). For instance, lung dysbiosis has been described in chronic obstructive pulmonary disease ( 46 ), lung cancer ( 47 ), interstitial lung disease ( 48 , 49 ), cystic fibrosis ( 50 , 51 ), asthma ( 52 ), acute respiratory distress syndrome, and ventilator-associated pneumonia ( 53 ), as well as infectious diseases, such as tuberculosis ( 54 ), and may be targeted for therapeutic intervention ( 55 ). In the context of fungal pneumonia, the lung microbiome has been investigated by bronchoalveolar lavage fluid collection in patients with proven or probable invasive pulmonary aspergillosis ( 56 ).…”

Section: The Lung As Final Destinationmentioning

confidence: 99%

From the nose to the lungs: the intricate journey of airborne pathogens amid commensal bacteria

Costantini

Nunzi

Romani

2022

American Journal of Physiology-Cell Physiology

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The recent COVID-19 pandemic has dramatically brought the pitfalls of airborne pathogens to the attention of the scientific community. Not only viruses, but also bacteria and fungi may exploit air transmission to colonize and infect potential hosts and be the cause of significant morbidity and mortality in susceptible populations. The efforts to decipher the mechanisms of pathogenicity of airborne microbes have brought to light the delicate equilibrium that governs the homeostasis of mucosal membranes. The microorganisms already thriving in the permissive environment of the respiratory tract represent a critical component of this equilibrium and a potent barrier to infection by means of direct competition with airborne pathogens or indirectly via modulation of the immune response. Moving down the respiratory tract, physicochemical and biological constrains promote site-specific expansion of microbes that engage in cross-talk with the local immune system to maintain homeostasis and promote protection. In this review, we critically assess the site-specific microbial communities that an airborne pathogen encounters in its hypothetical travel along the respiratory tract and discuss the changes in the composition and function of the microbiome in airborne diseases by taking fungal and SARS-CoV-2 infections as examples. Finally, we discuss how the technological and bioinformatics advancements may turn microbiome analysis into a valuable tool in the hands of clinicians to predict the risk of disease onset, the clinical course and the response to treatment of the individual patients in the direction of personalized medicine implementation.

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Therapeutic Targeting of the Respiratory Microbiome

Abstract: under its Clinician-Scientist Individual Research Grant (MOH-000141) (S.H.C.) and Clinician Scientist Award (MOH-000710) (S.H.C.). CSO/NRS Scottish Senior Clinical Fellowship award (SCAF/16/03) (D.B.). CSO/NRS Scottish Senior Clinical Fellowship award (SCAF/17/03) (J.D.C.

Cited by 41 publications

References 73 publications

The dynamic lung microbiome in health and disease

The dynamic lung microbiome in health and disease

Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota

From the nose to the lungs: the intricate journey of airborne pathogens amid commensal bacteria

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