Human Milk Microbiome: Associations with Maternal Diet and Infant Growth

Abstract

Human milk contains a complex and dynamic community of bacteria. These bacteria, through lactation, contribute significantly to establishing the infant gut microbiota, a critical contributor to establishing infant growth. One origin of the human milk microbiome (HMM) is the maternal gut microbiome, which is highly associated with the maternal diet. However, this association has not yet been explored among Indigenous populations or with the Guatemalan diet. Evidence supports shared bacterial strains between the maternal gut and milk microbiome and infant gut microbiome. However, the association between maternal diet during lactation and the HMM with early-life infant growth parameters has not yet been explored. In this dissertation, three studies were designed to explore the associations between the HMM at the species-level of Indigenous Mam-Mayan breastfeeding mothers in the Western Highlands of Guatemala with their (1) infants' head-circumference (HC) (2) infants' linear growth, and (3) the association between maternal dietary intakes and the HMM in two stages of lactation. The first manuscript explored whether the HMM of breastfeeding mothers was associated with their infants' head-circumference-for-age-z-score (HCAZ) as a proxy measure of brain growth. It also aimed to identify HMM species that were differentially abundant (DA) between infants with normal HCAZ versus infants with smaller HCAZ in two stages of lactation: early (6–46 days postpartum) and late (109–184 days postpartum). The richness of the HMM community differed within the HCAZ groups in early lactation, and differences identified were between the HCAZ groups in both early and late lactation. Several DA species between normal HCAZ and smaller HCAZ infants, including Streptococcus species of several human colonizers in the normal HCAZ infants. The smaller HCAZ had more DA species that were identified with environmental origin or potential pathogenicity. This study highlights the potential contribution of the HMM species to head growth. The second manuscript explored whether the HMM of the breastfeeding mothers in our study population was associated with their infants’ linear growth as length-for-age-z-score (LAZ) and weight as weight-for-age-z-score (WAZ). It also aimed to identify HMM species that were DA between infants with normal LAZ versus mildly stunted infants and between infants with normal WAZ versus infants with mild underweight in two stages of lactation: early and late. The HMM community differed between non-stunted and stunted infants and between infants with normal weight and infants with mild underweight in both stages of lactation. Mild growth faltering among breastfed infants was associated with greater opportunistic and pathogenic DA species in HMM, whereas the microbiome of infants with either normal LAZ or normal WAZ had a greater differential abundance of lactic acid bacteria. This study highlights the potential contribution of the HMM species to infant growth during the first six months of life. The third manuscript assessed the association between maternal dietary intakes during the first six months of lactation and the HMM DA species identified between infants with normal HCAZ versus infants with smaller HCAZ, between infants with normal LAZ versus mildly stunted infants, and between infants with normal WAZ versus infants with mild underweight. Several correlations between maternal dietary intakes with multiple DA species were identified between infants with normal growth and infants with mild growth faltering. The study provides substantial evidence of the potential association of maternal diet on breastfed infant growth via the HMM. Collectively, the three studies identified the complex interactions among maternal nutrient intakes during lactation, the milk microbiota, and infant growth. They highlighted an overlooked contribution of maternal diet during lactation on early-life infant growth through the modulation of the HMM.