DNA METHYLATION ALTERATIONS AND GUT DYSBIOSIS ASSOCIATED WITH PRETERM BIRTH: ROLE OF MATERNAL UNDERNUTRITION

Abstract

Preterm birth (PTB), defined as delivery before 37 weeks of gestation, is a leading cause of neonatal mortality. Recent studies highlighted diet as a risk factor for PTB. To date, no study has comprehensively examined how maternal undernutrition could be associated with PTB through underlying pathological mechanisms, such as alterations in both DNA methylation (DNAm) and gut microbiome composition. Therefore, this study aimed to investigate placenta and cord blood DNAm alterations in addition to gut microbiome changes in mothers and babies in the PTB group compared to full-term pregnancies by highlighting the association between maternal undernutrition and epigenetic and microbial changes. Clinical data and pregnancy outcomes were collected for 48 maternal-infant dyads (18 PTB vs. 30 full-term subjects) from the Karen or Burmese populations of Myanmar and Thailand. Nutrient intakes were computed based on 24-hour recalls and analyzed by the Nutritionist Pro™ software. DNAm was measured using the Infinium MethylationEPIC array and RnBeads analysis of 39 placental and 34 fetal cord blood samples. Gut microbiome analysis was conducted following 16s rDNA sequencing of 1,190 fecal samples using the QIIME2 pipeline. Our analysis revealed pan-undernutrition across several essential nutrients, particularly proteins, in mothers who experienced PTB compared to controls (P < 0.05). LIPF promoter hypomethylation (Δβ = -0.11776) and SSB promoter hypermethylation (Δβ = 0.19073) were associated with PTB in the placenta and cord blood, respectively (FDR-adjusted p-value 

Date of Award	2025
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences