Gut Eggerthella lenta aggravates chronic pulmonary infection through taurine ursodeoxycholic acid induced neutrophil dysfunction

The “gut-lung” axis is crucial for the chronic infection in bronchiectasis. However, the responsible microbe and the mechanism in the “gut-lung” axis of bronchiectasis are still in demand for precise elucidation. Here, we reported that <italic>Eggerthella lenta</italic> in the gut and taurine ursodeoxycholic acid (TUDCA) both in the gut and serum are enriched in patients with bronchiectasis and positively associated with bronchiectasis severity. Fecal microbiota transfer from bronchiectasis with high <italic>E. lenta</italic> aggravates pulmonary <italic>Pseudomonas aeruginosa</italic> infection in mice. Mechanistically, elevated <italic>E. lenta</italic>-derived TUDCA resulted in reduced phosphorylation of AMP-activated protein kinase (AMPK) and hampered ATP production. Ultimately, the neutrophils with impaired function dampened the elimination of <italic>P. aeruginosa</italic> in the lung and resulted in aggravated injury. These findings provides insights into an chronic pulmonary infection mechanism driven by gut microbiome and suggests that interventions with E. lenta or AMPK could complement prevention strategies for bronchiectasis. <fig><object-id>erj;64/suppl_68/OA3681/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <fig><object-id>erj;64/suppl_68/OA3681/F2</object-id><object-id>F2</object-id><object-id>F2</object-id><graphic></graphic></fig>