Maternal diet alters human milk oligosaccharide composition with implications for the milk metagenome

Abstract

Human milk is the optimal nutrition source for infants, and oligosaccharides represent the third most abundant component in milk after lactose and fat. Human milk oligosaccharides (HMO) are favorable macromolecules which are, interestingly, indigestible by the infant but serve as substrates for bacteria. Hypothesizing that the maternal diet itself might influence HMO composition, we sought to directly determine the effect maternal diet on HMO and the milk bacteria. Employing a human cross-over study design, we demonstrate that distinct maternal dietary carbohydrate and energy sources preferentially alter milk concentrations of HMO, including fucosylated species. We find significant associations between the concentration of HMO-bound fucose and the abundance of fucosidase (a bacterial gene that digests fucose moieties) harbored by milk bacteria. These studies reveal a successive mechanism by which the maternal diet during lactation alters milk HMO composition, which in turn shapes the functional milk microbiome prior to infant ingestion.

Priming for Life: Early Life Nutrition and the Microbiota-Gut-Brain Axis

“…Human milk oligosaccharides (HMOs) such as 2-fucosyllactose and lacto-N-tetraose, are indigestible glycans that pass through the GI tract. HMOs composition is affected by maternal characteristics such as maternal BMI and geography [ 198 ], genetics [ 199 ] and diet [ 200 ]. In a recent study, a short-term dietary intervention in lactating mothers induced significant alterations in the HMO composition, showing that dietary choices during lactation impacts HMOs rapidly [ 200 ].…”

“…HMOs composition is affected by maternal characteristics such as maternal BMI and geography [ 198 ], genetics [ 199 ] and diet [ 200 ]. In a recent study, a short-term dietary intervention in lactating mothers induced significant alterations in the HMO composition, showing that dietary choices during lactation impacts HMOs rapidly [ 200 ]. Upon reaching the intestines, HMOs are fermented by microbiota serving as prebiotics and, promoting microbial growth in a strain-specific manner [ 201 ].…”

“…For instance, a maternal Mediterranean diet led to increased abundance of Lactobacilli compared to Western diet, in the mammary glands of a non-human primate model [ 232 ]. In another recent human study maternal diet modified the HMO composition in breast milk and the metagenomic (but not taxonomic) landscape of milk bacteria as a response to dietary-related alterations of the HMOs in human milk [ 200 ]. These alterations in milk microbiota, link maternal nutrition to metabolic capacity of milk microbiota that are seeded to the infant gut.…”

“…These alterations in milk microbiota, link maternal nutrition to metabolic capacity of milk microbiota that are seeded to the infant gut. Maternal diet during lactation changes the metabolic capacity of her gut and breast milk microbiota that are subsequently seeded to the infant gut during lactation, leaving microbial and metabolic signatures during critical temporal windows of development [ 200 ].…”

“…As long as breastfeeding is maintained, breast milk microbiota is an endless supply of colonizing bacteria for the infant gut and exert their effects via the gut-brain axis on modulation of intestinal, neurological and behavioural functions in early life that could possibly imprint the CNS and immune system throughout the lifespan [ 5 , 121 , 233 ]. Diet remains the major regulator of both maternal and infant intestinal microbiota [ 63 ] as well as breast milk microbiota [ 121 , 200 ]. Some breastfeeding-related protective mechanisms on infants are also partially attributed to microbiota present in breast milk itself [ 121 ].…”