Lung-Gut Microbiota and Tryptophan Metabolites Changes in Neonatal Acute Respiratory Distress Syndrome

Abstract

Jingli Yang,1– 4 Yu He,1– 5 Qing Ai,1– 4 Chan Liu,1– 4 Qiqi Ruan,1– 4 Yuan Shi1– 4 1Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2National Clinical Research Center for Child Health and Disorders, Chongqing, People’s Republic of China; 3Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Neonatology, Jiangxi Hospital Affiliated to Children’s Hospital of Chongqing Medical University, Jiangxi, People’s Republic of ChinaCorrespondence: Yuan Shi, Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China, Email [email protected]: 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.Keywords: Neonatal acute respiratory distress syndrome, NARDS, lung microbiota, gut microbiota, tryptophan metabolites, correlation analysis, predictive diagnosis

Keywords

• neonatal acute respiratory distress syndrome
• nards
• lung microbiota
• gut microbiota
• tryptophan metabolites
• correlation analysis
• predictive diagnosis