432 - Alteration of Gut Microbiota in Preterm Infants with Patent Ductus Arteriosus: Implication for the Heart–Gut Axis

Publication Number: 3417.432

Teahyen Cha, Gangnam Severance Hospital, Seongdong-gu, Seoul-t'ukpyolsi, Republic of Korea; Min-Jin Kwak, Kookmin University, Seoul, Seoul-t'ukpyolsi, Republic of Korea; Gulam Mustafa, Hanyang University, Seoul, Seoul-t'ukpyolsi, Republic of Korea; Jae Yoon Na, Hanyang University College of Medicine, Seongdong-gu, Seoul-t'ukpyolsi, Republic of Korea; Byong-Hun Jeon, Hanyang University, Gwangjin-gu District, Seoul-t'ukpyolsi, Republic of Korea; Hyun-Kyung Park, Hanyang University College of Medicine, Seoul, Korea, Seoul, Seoul-t'ukpyolsi, Republic of Korea

Background: Patent ductus arteriosus (PDA) is common in preterm infants and can impact systemic circulation. Hemodynamically significant PDA (hsPDA) may disrupt intestinal perfusion, affecting gut microbiota development. Our previous study found hsPDA is associated with microbial dysbiosis, including Proteobacteria enrichment and reduced diversity, but the effects of PDA on microbiota dynamics remain unclear.

Objective: This study aims to examine longitudinal changes in gut microbiota in preterm infants with different PDA statuses (spontaneous closure, hsPDA, and delayed closure (dPDA)). We will assess the impact of PDA physiology on microbial diversity and maturation, and explore how hemodynamic instability affects gut microbial development.

Design/Methods: This study includes preterm infants born at Hanyang University Medical Center (March 2021-June 2024). Initial echocardiography was performed on days 3-5 after birth. Infants with open ductus underwent follow-up evaluations, while those with closed ductus were classified as control. Follow-up echocardiography was done within two weeks or earlier if symptoms developed. Infants were grouped into dPDA and hsPDA. Fecal samples were collected at meconium, 1 week, 1 month, and 2 months. Gut microbiota composition was assessed using 16S rRNA sequencing with Oxford Nanopore technology.

Results: A total of 44 preterm infants were included: hsPDA (6), dPDA (18), and control (19). No significant differences were found in demographic or clinical characteristics, except for sex (p = 0.021). hsPDA was associated with Proteobacteria enrichment, whereas dPDA and control showed balanced microbiota compositions. Alpha diversity increased over time in all groups, with hsPDA showing delayed maturation. At the genus level, hsPDA exhibited early overgrowth of Klebsiella and Enterococcus, while dPDA and control showed commensal-dominant microbiota. Beta diversity analysis revealed distinct clustering of hsPDA from dPDA and control groups (FDR < 0.01). Network analysis showed that hsPDA infants had a less resilient microbial network, indicating greater vulnerability to dysbiosis, while the control group exhibited a more stable microbial network.

Conclusion(s): hsPDA is linked to early microbial dysbiosis and delayed maturation, which gradually transitions to a more balanced microbiota. In contrast, dPDA and control groups exhibit stable microbial development. These findings suggest that hemodynamic instability in hsPDA disrupts gut microbiota colonization. Future analyses will focus on metabolites to further investigate the functional impact of these microbial changes in preterm infants.

Baseline demographic and clinical characteristics of the study population
A total of 44 preterm infants were included: hsPDA (n = 6), dPDA (n = 18), and control (n = 19). No significant differences were observed among groups in gestational age, birth weight, or major morbidities, except for sex distribution (p = 0.021).
Abbreviations: hsPDA, hemodynamically significant patent ductus arteriosus; dPDA, delayed closure PDA; RDS, respiratory distress syndrome; NEC, necrotizing enterocolitis; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; HIE, hypoxic-ischemic encephalopathy; BPD, bronchopulmonary dysplasia; ROP, retinopathy of prematurity.

Longitudinal changes in gut microbial composition by PDA status
(A) Relative abundance of bacterial taxa at the phylum level in infants with hsPDA, dPDA, and control groups. hsPDA infants showed early enrichment of Proteobacteria and depletion of Firmicutes compared with other groups.
(B) Relative abundance at the genus level. hsPDA infants exhibited early overgrowth of Klebsiella and Enterococcus, whereas the dPDA and control groups maintained a balanced community dominated by commensal genera such as Lactobacillus, Veillonella, and Blautia.
Abbreviations: hsPDA, hemodynamically significant patent ductus arteriosus; dPDA, delayed closure PDA; CON, control; WK, week; Mo, month.

Network analysis of gut microbiota by PDA status over time.
Microbial association networks were constructed at the genus level for infants with hsPDA, dPDA, and control groups during three postnatal periods (D0-2 W, 2 W-1 M, and 1 M-2 M). Each node represents a bacterial genus, and edges indicate significant correlations between taxa. hsPDA infants exhibited a simpler and more centralized network, indicating reduced microbial diversity and resilience, whereas dPDA and control groups maintained more complex, interconnected, and balanced microbial networks over time.
Abbreviations: hsPDA, hemodynamically significant patent ductus arteriosus; dPDA, delayed closure PDA; CON, control; D, day; W, week; M, month.