Geographic variation of the microbiome-resistome in bronchiectasis: Data from the European Bronchiectasis Registry (EMBARC)

<bold>Introduction:</bold> Bronchiectasis in Europe exhibits geographic variation in sputum microbiology, however, the additive value of metagenomic sequencing remains unexplored. <bold>Methods:</bold> Bronchiectasis sputum (N=349) from 3 European regions (Northern and Western Europe (NWE), Southern Europe (SE), and the UK) recruited through EMBARC were interrogated by shotgun metagenomics to evaluate microbiomes and resistomes. <bold>Results:</bold> The microbiome exhibits significant geographic variation across Europe with top discriminant microbes as follows: <italic>Pseudomonas aeruginosa</italic> (SE), <italic>Haemophilus influenzae</italic> (UK) and <italic>Gemella sanguinis</italic> (NWE) (PERMANOVA<0.001), similar to culture. Similarly, resistomes exhibit increased multidrug resistance in SE and NWE and tetracycline resistance in the UK (PERMANOVA<0.001). Previously established bronchiectasis resistotypes (RT) (Mac Aogain et al, AJRCCM 2024) were recapitulated with highest occurrence of the more severe RT2 in SE (42%; n=67 vs 27%; n=10 NWE vs 10%; n=12 UK; p<0.001). Importantly, <italic>Pseudomonas</italic> associates with RT2 genes and <italic>Streptococcus</italic> and <italic>Haemophilus</italic> with RT1 genes irrespective of geography. <bold>Conclusion:</bold> The microbiome, resistome and resistotypes in bronchiectasis across Europe exhibits geographic variation, however, key pathogens harbour similar resistance genes across regions, supporting unified treatment approaches. <bold>Funding:</bold> This work is supported by the Singapore Ministry of Health’s NMRC under the Clinician-Scientist Individual Research Grant MOH-001356 (S.H.C.), a Clinician-Scientist Award MOH-000710 (S.H.C) and EMBARC3. EMBARC3 is funded by the European Respiratory Society through the EMBARC3 clinical research collaboration.