Gut-lung axis in neonatal respiratory distress syndrome: integrated evidence from pharmacovigilance and Mendelian randomization

doi:10.5246/jcps.2026.07.046

Abstract

Abstract:

Neonatal respiratory distress syndrome (NRDS) is a major cause of neonatal morbidity and mortality and is closely linked to prematurity, surfactant deficiency, and inflammatory processes. Emerging evidence suggests that the gut microbiota and inflammatory cytokines may modulate NRDS through the gut-lung axis; however, the underlying causal relationships remain incompletely understood. In the present study, we integrated pharmacovigilance data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) with bidirectional and mediation Mendelian randomization (MR) analyses to investigate the roles of drug exposure, gut microbiota, and inflammatory cytokines in NRDS. FAERS data spanning 2004 to 2024 identified 162 drugs significantly associated with NRDS risk, including antibiotics, systemic hormones, and immunomodulatory agents. MR analyses revealed that increased abundances of CAG-177 sp003514385 and Chromatiales were associated with elevated plasma levels of latency-associated peptide transforming growth factor beta 1 (LAP-TGF-β1) and CUB domain-containing protein 1 (CDCP1), both of which exhibited protective effects against NRDS. In contrast, increased abundance of Syntrophomonadia was associated with a higher risk of NRDS, although elevated CDCP1 levels partially mitigated this effect. Sensitivity analyses supported the robustness of these findings. Overall, this study provided novel evidence linking drug exposure, gut microbiota dysbiosis, inflammatory cytokine signaling, and NRDS risk, and identified LAP-TGF-β1 and CDCP1 as potential biomarkers and therapeutic targets, highlighting the promise of microbiota- and cytokine-targeted strategies for the prevention and management of NRDS.

Key words: Neonatal respiratory distress syndrome, Gut microbiota, Inflammatory cytokines, Mendelian randomization, Gut-lung axis, Microbiota-targeted therapy

Supporting: /attached/file/20260809/20260809005100_145.pdf

Yixiao Zhu, Li Lin, Lijing Yang, Chengqian Teng, Lirong Zhang, Andi Chen, Xiaoxia Wei, Xiaohui Chen. Gut-lung axis in neonatal respiratory distress syndrome: integrated evidence from pharmacovigilance and Mendelian randomization[J]. Journal of Chinese Pharmaceutical Sciences, 2026, 35(7): 643-657.

Figures/Tables 8

Table 1.

Table 2. Summary table of mediating inflammatory cytokines.

Table 3. Summary of effect (beta).

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