Background: Emerging evidence suggests a cross-talk between gut microbiota and respiratory health, particularly in asthma and type 2 inflammation. Despite this, large-scale studies to support these findings are lacking. Aim: This project aims to investigate the relationships between gut microbiota, type-2 inflammatory biomarkers, asthma phenotypes, and lung function in a large, well-characterized multi centre cohort. Methods Study population: This cross-sectional study will utilize data from approximately 8000 participants, aged 50 to 65, from the SCAPIS Malmö and Uppsala study centres. Participants completed detailed questionnaires on lifestyle and health history and underwent clinical examinations, including spirometry and diffusing capacity (DLCO) testing. Lung function measurements and inflammatory biomarkers: Asthma phenotypes will be classified as type-2-low or type-2-high based on biomarker levels. Lung function has been assessed using spirometry, with key measures including FEV1/FVC < LLN, FEV1 < 80% of predicted values based on GLI reference values and z-scores and DLCO data. Type-2 biomarkers such as eosinophil counts (EOS), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and fractional exhaled nitric oxide (FeNO) have been measured. Microbiome Analysis: Fecal samples were collected by participants at home, stored in home freezers, and later transported to Clinical Microbiomics A/S (Copenhagen, Denmark) for processing. Metagenomic DNA extraction, library preparation, and sequencing were performed using the Illumina NovaSeq 6000 platform. Bioinformatics processing and taxonomic annotation has been conducted to define metagenomic species. Alpha diversity will be estimated using the Shannon diversity index, inverse Simpson index, and species richness. Beta diversity will be assessed using Bray-Curtis dissimilarity. Statistical Analysis: Associations between gut microbiota species abundance, type-2 inflammatory biomarkers, asthma phenotypes, and lung function will be evaluated using ordinary and multivariable regression models. Confounding variables will be identified and adjusted for using directed acyclic graphs (DAGs). Multiple testing corrections will be applied using the Benjamini-Hochberg false discovery rate at 5%. Potential research outcomes: This project aims to identify specific gut microbiota phyla associated with type-2 inflammatory markers and distinct asthma phenotypes. We expect to find correlations between certain gut microbiota species and lung function measurements. Identifying gut microbiota profiles associated with type-2-high asthma could enhance our understanding of the gut-lung axis and its role in respiratory health, potentially fuelling research for novel diagnostic and therapeutic approaches for asthma and other respiratory diseases. By addressing these objectives, this research will significantly contribute to the limited body of knowledge on the gut microbiome's impact on lung health, offering insights that could inform future clinical practices and public health strategies. Ethics: The Swedish Ethical Review Authority approved the SCAPIS study (DNR 2010-228-31M). All participants provided written informed consent.