328 - Microbiome Analysis and Inflammatory Mediators: Association with Bronchopulmonary Dysplasia in Extremely Preterm Infants

Publication Number: 1312.328

Baek Sup Shin, Seoul National University Children's Hospital, Jongno-gu, Seoul-t'ukpyolsi, Republic of Korea; Ee-Kyung Kim, Seoul National University Children's Hospital, Seoul, Seoul-t'ukpyolsi, Republic of Korea; Seung Han Shin, Seoul National University Children's Hospital, Seoul, Seoul-t'ukpyolsi, Republic of Korea; Eunha Kim, Korea University, Seongbuk-gu, Seoul-t'ukpyolsi, Republic of Korea; Ju Sun Heo, Seoul National University College of Medicine, Seoul, Seoul-t'ukpyolsi, Republic of Korea

Background: The microbiome of preterm infants can differ from that of term infants due to exposure to intrauterine infections or maternal antibiotic use at birth. In addition, the immune system of preterm infants is immature, which makes them more susceptible to dysbiosis. Given that Bronchopulmonary Dysplasia (BPD) can be attributed to immaturity and inflammation, it is reasonable to assume a correlation between the microbiome and BPD. Additionally, molecules such as short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS) can be transported to the lungs through the bloodstream and affect lung development and inflammatory processes.

Objective: The aim is to verify whether the microbiota in preterm infants impacts the development of BPD. Additionally, we will explore the role of short-chain fatty acids (SCFAs) in this process.

Design/Methods: In a prospective cohort study, preterm infants born at gestational ages less than 28 weeks were included. Stool and blood specimens were collected at four specific time points: immediately after birth, two weeks post-birth, at a postmenstrual age (PMA) of 31+0 to 31+6 weeks, and at a PMA of 35 to 38 weeks. Microbiome analysis was conducted using 16S rRNA amplicon sequencing. SCFAs, cytokines, and LPS in both blood and stool samples were measured. BPD was defined as moderate-to-severe BPD (MS-BPD) based on NICHD 2001 criteria. Logistic regression models were used to assess the association between microbiome diversity/mediators and MS-BPD, adjusting for gestational age (GA).

Results: A total of 39 infants were analyzed. Infants who developed MS-BPD (N=22) showed significantly lower fecal microbiome alpha diversity at 4 weeks of age compared to those without MS-BPD (N=17). This association remained strong even after adjusting for gestational age. Simpson index (Adjusted OR 0.574, 95% CI [0.391, 0.842], p=0.004) and lower Shannon index (Adjusted OR 0.002, 95% CI [0.000, 0.145], p=0.005) were significantly associated with an increased risk of MS-BPD. In contrast, fecal and plasma SCFA levels measured at all four time points showed no significant association with MS-BPD after adjusting for GA. However, positive association was observed between 4-week LPS levels and MS-BPD (Adjusted OR 1.002, 95% CI [1.000, 1.004], p=0.048).

Conclusion(s): Gut microbiome dysbiosis is strongly associated with the development of MS-BPD, independent of gestational age. It is plausible that a robust gut microbiome, characterized by high alpha diversity, coupled with a low systemic inflammatory burden (such as low LPS levels), constitutes a key anti-inflammatory axis protective against BPD