Defining the role and therapeutic manipulation of the gut-lung axis in respiratory disease

Project Member(s): Hansbro, P., Faiz, A., Liu, G.

Funding or Partner Organisation: National Health & Medical Research Council (NHMRC Synergy Grants)
National Health & Medical Research Council (NHMRC Synergy Grants)

Start year: 2022

Summary: Lung diseases are enormous clinical issues and effective treatments are urgently needed. They are driven by local and systemic inflammation but the majority of studies only focus on the lung. There is infectious and immune crosstalk between the gut and lungs. Gut diseases induce lung inflammation and are linked to asthma and COPD, and vice versa. New approaches that manipulate gut microbiomes/metabolites and immunity have enormous potential as new therapies for lung diseases. We will synergise our skills to progress our pioneering studies of the gut-lung axis (GLA) to therapeutically manipulate microbiomes and immunity in the gut to treat lung diseases. 1 & 2 Define & manipulate the GLA in lung disease: We will use our unique mouse models of COPD, severe asthma and infections (flu, COVID-19) to assess changes in gut and lung microbiomes/metabolites, and translate findings to lung disease patients. In our models we will define maximally effective gut microbiome/metabolite interventions with microbial transfers, pre/pro-biotics and antibiotics, and dietary interventions designed at the molecular level to induce specific changes. 3 Clinical trials of GLA therapies in COPD: We will test novel and effective gut-targeted therapies in COPD in adaptive clinical trials, commencing with inulin supplements versus novel diets. We will assess detailed induced-sputum and lung function analysis in 1 centre with general analysis in others. Selected microbiomes/metabolites will be assessed and reverse translated into #2 to define cause and effect. 4 Multi-‘omics will link microbiome/metabolome changes to transcriptional/proteomic changes to create a holistic role for the GLA. We will define effective gut interventions for lung diseases that can progress in future large clinical trials for some of the most important and intractable diseases. We will establish a structural platform of adaptive clinical trials for respiratory diseases that can be expanded to gut and other diseases.

Publications:

Chen, H, Galvao, I, Donovan, C, Kim, R, Ortega, D & Hansbro, P 1970, 'Spatial transcriptomics mapped regions in lungs upon cigarette smoking', RESPIROLOGY, WILEY, pp. 121-121.

FOR Codes: Respiratory diseases , Respiratory System and Diseases (incl. Asthma), Treatment of human diseases and conditions