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Microbial Dysregulation of the Gut-Lung Axis in Bronchiectasis
Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis. Prospective and concurrent sampling of gut (stool) and lung (sputum) was performed in a cohort of = 57 individuals with bronchiectasis and subjected to bacteriome (16S rRNA) and m...
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Published in: | American journal of respiratory and critical care medicine 2023-04, Vol.207 (7), p.908-920 |
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Main Authors: | , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis.
Prospective and concurrent sampling of gut (stool) and lung (sputum) was performed in a cohort of
= 57 individuals with bronchiectasis and subjected to bacteriome (16S rRNA) and mycobiome (18S Internal Transcribed Spacer) sequencing (total, 228 microbiomes). Shotgun metagenomics was performed in a subset (
= 15; 30 microbiomes). Data from gut and lung compartments were integrated by weighted similarity network fusion, clustered, and subjected to co-occurrence analysis to evaluate gut-lung networks. Murine experiments were undertaken to validate specific
driven gut-lung interactions.
Microbial communities in stable bronchiectasis demonstrate a significant gut-lung interaction. Multibiome integration followed by unsupervised clustering reveals two patient clusters, differing by gut-lung interactions and with contrasting clinical phenotypes. A high gut-lung interaction cluster, characterized by lung
, gut
, and gut
, is associated with increased exacerbations and greater radiological and overall bronchiectasis severity, whereas the low gut-lung interaction cluster demonstrates an overrepresentation of lung commensals, including
,
, and
with gut
. The lung
gut
relationship, observed in the high gut-lung interaction bronchiectasis cluster, was validated in a murine model of lung
infection. This interaction was abrogated after antibiotic (imipenem) pretreatment in mice confirming the relevance and therapeutic potential of targeting the gut microbiome to influence the gut-lung axis. Metagenomics in a subset of individuals with bronchiectasis corroborated our findings from targeted analyses.
A dysregulated gut-lung axis, driven by lung
, associates with poorer clinical outcomes in bronchiectasis. |
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ISSN: | 1073-449X 1535-4970 |
DOI: | 10.1164/rccm.202205-0893OC |