While inflammation is key to our body’s defence against pathogens, an uncontrolled pro-inflammatory reaction can lead to tissue deterioration and ultimately death. Chronic lung inflammation is the main driver of pathogenesis in patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). In COPD patients, chronic lung inflammation is mainly triggered by cigarette smoke exposure, while in CF patients this is due to chronic infections. Currently, there is no safe and effective anti-inflammatory treatment for the COPD/CF population. In this project, I propose microbiome-based therapeutics as a novel anti-inflammatory treatment. To this end, two approaches will be used: (i) by designing anti-inflammatory consortia using a mixture of recently discovered anti-inflammatory bacteria, (ii) by identifying anti-inflammatory consortia using patient samples with low inflammatory profiles. Both approaches will be evaluated in in vivo-like models of CF/COPD bronchial epithelium, and further validated using mouse models. Finally, an aerosol therapy for delivery of anti-inflammatory consortia in mouse lungs will be optimized. With the high need of CF/COPD patients for anti-inflammatory treatments and the strong interest of pharmaceutical companies in anti-inflammatory drug development and microbiome-based therapeutics, it is anticipated that the outcomes of this project will be of significant value for the pharmaceutical sector and the end user.