Towards airway microbiome engineering for improving respiratory health

Kelsey E. Hern, Arthur Prindle*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

The known roles of human-associated microbes in health and disease have expanded in recent years. While the gut microbiome is the most well studied, the airway microbiome is gaining attention as an important gatekeeper of respiratory health. Compared to the gut, the airway microbiome has lower species complexity, greater niche stability, and represents an immediate point of contact with the outside world. These features make it an attractive target for improving respiratory health. As respiratory disease continues to increase among humans, it will be critical to develop novel approaches to combat new and emergent bacterial infections, viruses, and cancers for which we do not currently have treatments. This review seeks to define strategies for airway microbiome engineering—the intentional manipulation of airway associated microbes to restore species balance, enhance protective functions, or treat disease. We summarize the growing body of literature linking the airway microbiome to respiratory health and discuss both broad-spectrum and high precision technologies that hold particular promise for further development. We argue that inhaled probiotics and bacteriophage are among the most attractive technologies for clinical translation of airway microbiome engineering to improve respiratory health.

Original languageEnglish (US)
Article number115662
JournalAdvanced Drug Delivery Reviews
Volume225
DOIs
StatePublished - Oct 2025

Funding

We thank S. Quillin, K. Sneh, B. Everett and H. Hirsch for their helpful feedback on the manuscript. We are grateful for generous support from the David and Lucile Packard Foundation ( 2018-68055 ), the Army Research Office ( W911NF-19-1-0136 ), Pew Charitable Trusts ( 2019-A-06953 ), the National Science Foundation ( NSF 2239567 ), National Institute of General Medical Sciences of the National Institutes of Health ( 1R35GM147170-01 ) and ARPA-H ( 75N99223S0001 ).

Keywords

  • Bacteriophage
  • Microbiome engineering
  • Probiotics
  • Respiratory microbiome
  • Synthetic biology
  • Therapeutics

ASJC Scopus subject areas

  • Pharmaceutical Science

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