The Associations between Maternal Milk Microbiome, Oligosaccharides and Infant Gut Microbiota: Insights from a Burkinabe Cohort Study

Abstract Background: Human milk feeding supports infant development and protects against diseases, potentially through human milk oligosaccharides (HMOs) and milk-associated bacteria. However, the dynamics of milk microbiome and HMO composition, and their impact on infant gut microbiota in low- and middle-income countries remain underexplored, especially in the context of maternal nutritional challenges. Methods: We analyzed fecal and milk samples from 152 mother-infant pairs in Burkina Faso participating in a maternal nutrition intervention. Maternal gut microbiota were assessed using metagenomic sequencing during pregnancy (second and third trimester) and lactation (1-2 and 5-6 months postpartum) and infant gut microbiota were profiled at 1-2 and 5-6 months. Milk microbiome and HMO composition were analyzed with 16S rRNA sequencing and HPLC, respectively, at 14-21 days, 1-2, and 3-4 months postpartum. Results: Infant gut microbiomes at 1-2 months clustered into three patterns: Bifidobacterium-dominated, Escherichia-dominated, and a diverse group. These patterns converged by 5-6 months due to exclusive breastfeeding. Maternal gut microbiota at trimester 3 strongly correlated with infant gut microbiota, but postnatal maternal samples did not. Milk microbiome diversity mirrored infant gut clusters at 3-4 months, with temporal correlations evident only at matching time points. Infant gut Bifidobacterium species correlated with fucosylated HMOs, such as 2’Fucosyllactose (2′FL) at early time point, and correleated with sialylated HMOs later. Redundancy analysis revealed that HMOs were significant drivers of infant gut microbiota variance, surpassing milk microbiome contributions. Conclusions: Optimizing maternal nutrition to enhance HMO profiles may foster healthier infant gut microbiota development in resource-limited settings. Funding source: This work is supported by the Bill & Melinda Gates Foundation [OPP1175213]. Presented at: The 22nd International Society for Research in Human Milk and Lactation (ISRHML) Conference December 9th – 13th, 2024, Hyatt Place, Charleston, South Carolina, USA Presenting Author: Lishi Deng, MSc, PhD student Email: [email protected]