“Integrative microbiomics” reveals a disrupted interactome in bronchiectasis exacerbations

Background: To date, no study has integrated bacterial, viral and fungal microbiomes to provide a holistic assessment of the true in-vivo state. Methods: We report the first integrated ‘multi-biome’ analysis integrating bacteriome, virome and mycobiomes in bronchiectasis (n=217) employing weighted Similarity Network Fusion coupled to co-occurrence network analysis to evaluate the ‘interactome’. Interactome dynamics at baseline, during exacerbations and following recovery was assessed in n=17 patients with bronchiectasis. Results: “Integrative microbiomics” identifies patients at high-risk of exacerbation. Frequent exacerbators exhibit reduced α-diversity and elevated antagonistic interactions. Assessment of the Pseudomonas-interactome reveals that its network rather than abundance is key in determining exacerbation risk. Longitudinal ‘interactome’ analysis reveals increased antagonistic interactions during exacerbations which resolve following treatment within an otherwise stable microbiome. The interactome has ‘core’ and ‘ancillary’ components, the latter altered during exacerbation. Conclusion: “Integrative microbiomics” captures interactions determining exacerbation risk otherwise unaccounted by specific microbes. Antibiotic strategies likely target interaction networks rather than individual microbes providing fresh approaches to understanding respiratory infection. Funding: Singapore Ministry of Health’s National Medical Research Council under its Transition Award (NMRC/TA/0048/2016) (S.H.C); Clinician-Scientist Individual Research Grant (MOH-000141) (S.H.C) and the NTU Integrated Medical, Biological and Environmental Life Sciences (NIMBELS) [NIM/03/2018] (S.H.C).