A gut Eggerthella lenta–derived metabolite impairs neutrophil function to aggravate bacterial lung infection

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 Eggerthella lenta 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 E. lenta aggravates pulmonary Pseudomonas aeruginosa infection in mice. Mechanistically, elevated E. lenta-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 P. aeruginosa in the lung and resulted in aggravated injury. These findings indicate that E. lenta and TUDCA aggravate chronic pulmonary infection, providing insights into microbe-mediated gut-lung crosstalk in bronchiectasis.