Systematic identification of phage-host cross-talk in airway microbiome and its role in asthma

• Applicant: Professorin Dr. Li Deng
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Clinical Immunology and Allergology ; Microbial Ecology and Applied Microbiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514085143

Asthma is a complex airway disease in which genetic factors interact with environmental exposures and microbial stimuli such as viruses and bacteria. While dysbiosis of the airway microbiome with the preponderance of Proteobacteria has been linked to asthma development and exacerbations, farm environments were demonstrated to protect from airway colonization with e.g. Moraxella and asthma. The underlying mechanisms, however, remain still unclear. Phage communities (phageome) are emerging as fundamental drivers profoundly shape microbial populations and processes that go beyond mortality of microbes and horizontal gene transfer, regarding many endpoints including allergy, as well as in microenvironments such as mucosa. We hypothesize that phages affect airway dysbiosis and thereby contribute differentially to asthma risk in farm and non-farm environments. Our main goal is to develop a systematic understanding of cross-talk between phageome and microbiome in the airway and their impact to asthma. We aim to characterize the role of the upper airway phageome in asthma protective environments (Aim1), to defining the role of phage-host interactions in the upper airway of asthma protective environments (Aim2), and to decipher the molecular mechanisms phages use to regulate the bacterial communities of the upper airway and its relevance to asthma prevention (Aim3). If our hypothesis can be verified, due to their high host specificity, a novel targeted asthma therapy could be developed based on a precisely designed phageome specifically target asthma associated dysbiosis microbiota. We will achieve this goal by employing i) our recent advances in cultivation-independent but host-targeted, single-phage technology which allow us to achieve targeted phageome of a bacteria; and ii) a unique multicentre cohort PASTURE where 1,133 children were recruited (half are farm children) with comprehensive clinical characterization.

• DFG Programme: Research Grants