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Detection of bile acids in bronchoalveolar lavage fluid defines the inflammatory and microbial landscape of the lower airways in infants with cystic fibrosis.
Caparrós-Martín, Jose A; Saladie, Montserrat; Agudelo-Romero, S Patricia; Reen, F Jerry; Ware, Robert S; Sly, Peter D; Stick, Stephen M; O'Gara, Fergal.
Afiliação
  • Caparrós-Martín JA; Wal-Yan Respiratory Research Centre, Telethon Kids Institute, Perth, WA, Australia.
  • Saladie M; Curtin Health Innovation Research Institute (CHIRI), Curtin University, Perth, WA, Australia.
  • Agudelo-Romero SP; Curtin Health Innovation Research Institute (CHIRI), Curtin University, Perth, WA, Australia.
  • Reen FJ; Present Address: Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira I Virgili-EURECAT, Reus, Spain.
  • Ware RS; Wal-Yan Respiratory Research Centre, Telethon Kids Institute, Perth, WA, Australia.
  • Sly PD; The University of Western Australia, Perth, WA, Australia.
  • Stick SM; School of Microbiology, University College Cork, Cork, Ireland.
  • O'Gara F; Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland.
Microbiome ; 11(1): 132, 2023 06 13.
Article em En | MEDLINE | ID: mdl-37312128
BACKGROUND: Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota. RESULTS: Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage. CONCLUSIONS: Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. Video Abstract.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose Cística Tipo de estudo: Clinical_trials / Diagnostic_studies Limite: Humans / Infant Idioma: En Revista: Microbiome Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Austrália País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose Cística Tipo de estudo: Clinical_trials / Diagnostic_studies Limite: Humans / Infant Idioma: En Revista: Microbiome Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Austrália País de publicação: Reino Unido