Post partum gut microbiome signatures and prematurity in low resource settings of Pakistan

Over fifteen million babies are born preterm globally each year, with 81% occurring in LMICs, significantly impacting health, and quality of life. Preterm birth (PTB) displays multifactorial aetiologies, including microbial influences on the maternal gut microbiome. Characterizing maternal gut microbiome signatures associated with PTB can provide insights into postpartum microbial patterns and their potential relevance to maternal and neonatal health. This study explores the maternal gut microbial diversity in low-resource settings of Pakistan (LMIC), aiming to identify postpartum microbiome associations with PTB. To explore the relationship between the gut microbiome and PTB, we conducted a cross-sectional case-control comparative gut microbiome analysis on a subset of the AMANHI fecal biobank who met strict inclusion criteria (term = 61, preterm = 47). After reads underwent QC-filtering and de-hosting, we retained only species present in at least 5% of the samples with a mean proportion of ≥ 1e-5 for downstream analysis. The non-parametric statistical hypothesis test (Wilcoxon) on maternal gut microbiome richness and evenness (Shannon index) revealed that the preterm cohort exhibits significantly higher α microbial diversity compared to the term cohort. Notably, Prevotella copri, Bifidobacterium adolescentis, Lactobacillus ruminis, and Faecalibacterium prausnitzii stood out as the four most abundant species across all samples. Microbiome differential analysis showed several species of the genera Prevotella and E. coli as differentially abundant across term and preterm cohorts, indicating distinct maternal gut microbiome signatures associated with PTB. Randon Forest Classification (RFC) modelling found P. copri as the most important microbial signature for preterm/term discrimination. Specifically, the RFC analyses showed that a relative abundance of P. copri < 0.13 in the maternal gut microbiome was strongly associated with PTB status in this postpartum dataset. These findings provide a foundation for future studies exploring microbiome-targeted interventions in LMICs, such as, Pakistan.