Dysregulation of the microbial ‘gut-lung’ axis in bronchiectasis

<b>Introduction:</b> Emerging work supports the existence of a microbial 9gut-lung9 axis which remains unexplored in bronchiectasis. <b>Methods:</b> Prospective and concurrent sampling of sputum (lung) and stool (gut) in a bronchiectasis cohort (n=57) was performed and subjected to bacteriome (16S rRNA) and mycobiome (18S ITS) assessment. Shotgun metagenomics was performed in a subset (n=15). Data from lung and gut compartments were integrated by weighted similarity network fusion (wSNF) followed by spectral clustering and co-occurrence analysis to assess clinically relevant 9gut-lung9 networks. <b>Results:</b> We report the first description of a 9gut-lung9 axis in bronchiectasis. Microbial communities demonstrate greater fungal overlap but reduced bacterial diversity between the lung and gut, respectively. Multi-biome integration followed by clustering reveals a 9high-risk9 patient group characterised by severe clinical and radiological bronchiectasis including increased exacerbations. These patients exhibit enhanced 9gut-lung9 microbial interactions and significant increases in airway <i>Pseudomonas</i> accompanied by gastrointestinal <i>Bacteroides</i> and <i>Saccharomyces.</i> Profiles of the 9low-risk9 group were characterized by oral commensals. <b>Conclusion:</b> A dysregulated 9gut-lung9 axis associates with poorer clinical outcome in bronchiectasis. Immunomodulation of the 9gut-lung9 axis in bronchiectasis warrants further assessment. <b>Funding:</b> Singapore Ministry of Health9s National Medical Research Council under its Clinician-Scientist Individual Research Grant (MOH-000141) (S.H.C) and Clinician Scientist Award (MOH-000710) (S.H.C).