Abstract
Purpose
Neonatal Acute Respiratory Distress Syndrome (NARDS) is a severe respiratory crisis threatening neonatal life. We aim to identify changes in the lung-gut microbiota and lung-plasma tryptophan metabolites in NARDS neonates to provide a differentiated tool and aid in finding potential therapeutic targets.
Patients and Methods
Lower respiratory secretions, faeces and plasma were collected from 50 neonates including 25 NARDS patients (10 patients with mild NARDS in the NARDS_M group and 15 patients with moderate-to-severe NARDS in the NARDS_S group) and 25 control patients screened based on gestational age, postnatal age and birth weight. Lower airway secretions and feces underwent 16S rRNA gene sequencing to understand the microbial communities in the lung and gut, while lower airway secretions and plasma underwent LC-MS analysis to understand tryptophan metabolites in the lung and blood. Correlation analyses were performed by comparing differences in microbiota and tryptophan metabolites between NARDS and control, NARDS_S and NARDS_M groups.
Results
Significant changes in lung and gut microbiota as well as lung and plasma tryptophan metabolites were observed in NARDS neonates compared to controls. Proteobacteria and Bacteroidota were increased in the lungs of NARDS neonates, whereas Firmicutes, Streptococcus, and Rothia were reduced. Lactobacillus in the lungs decreased in NARDS_S neonates. Indole-3-carboxaldehyde decreased in the lungs of NARDS neonates, whereas levels of 3-hydroxykynurenine, indoleacetic acid, indolelactic acid, 3-indole propionic acid, indoxyl sulfate, kynurenine, and tryptophan decreased in the lungs of the NARDS_S neonates. Altered microbiota was significantly related to tryptophan metabolites, with changes in lung microbiota and tryptophan metabolites having better differentiated ability for NARDS diagnosis and grading compared to gut and plasma.
Conclusion
Significant changes occurred in the lung-gut microbiota and lung-plasma tryptophan metabolites of NARDS neonates. Alterations in lung microbiota and tryptophan metabolites were better discriminatory for the diagnosis and grading of NARDS.
Data Sharing Statement
The raw data supporting the conclusions of this article will be made available by the corresponding author YS, without undue reservation.
Ethics Approval and Consent to Participate
The sample collection and analysis from human was approved by the ethics committee of the Children’s Hospital of Chongqing Medical University.
Consent for Publication
All authors gave their consent for publication.
Acknowledgments
Dr Yang thanked Mr. Bo Lu for his help and support during the experiment.
Author Contributions
All authors have contributed significantly to the reported work, including conception, study design, execution, data acquisition, analysis, and interpretation. Additionally, all authors have reached an agreement on the journal to which the article has been submitted and accept responsibility for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.