Human milk oligosaccharides and association with infants' Growth

Human milk is the recommended and sole nutrient source for newborns, adapted by evolution to provide both nutrition and protection. In maternal milk, some nutrients such as vitamins and fatty acids vary depending on the dietary intake of the lactating mother, while others are primarily under genetic control. After lactose and fat, one of the largest compound groups of mass in human milk is oligosaccharides (HMOs), with slightly higher concentrations than protein. These generally non-digestible oligosaccharides are elongations of the milk sugar lactose with combinations of galactose, N-acetyl-glucosamine, fucose and/or sialic acid.. The similarity of HMOs with mucosal glycans, together with numerous basic research data suggest that HMOs affect the establishment of mucous adapted commensals, adherence of pathogens to the epithelium and mucosal cell reactivity, thereby possibly providing protection from infections. Through research in the past, it has been established that the major constituents of HMOs are determined by the mother genotype for the fucosyltransferases 2 (FUT2, secretor) gene.

The prevalence of FUT2 enzyme activity within the population has been proven to vary strongly depending on geography. In most geographic regions functional FUT2 alleles are predominant by over 70%, while in some regions of Asia and Africa non-functional FUT2 alleles were reported equally prevalent. Human microbial and viral interactions, in particular with pathogens, are likely evolutionary forces that could have driven changes in the make-up of FUT2: loss of functional FUT2 activity has been associated with better resistance to some pathogens such as specific Norovirus genotypes, with the trade-off being a higher risk for infections by other pathogens affecting the respiratory, urinary tract or the gastro-intestinal systems. Non-functional FUT2 genotypes have also been associated with higher risk for type 1 diabetes, Crohn’s disease and neonatal sepsis.

Thus, it is important to discover more about these components of human milk, which look like they can enhance infant immune development and provide protection from infection as well as contributing to infant weight and body composition. A new study at the National University of Singapore, published in February 2017, set out to investigate the dependence of several major representative HMOs on the FUT2 status with infant growth up to four months of life. Looking at breastmilk samples from lactating mothers on a regular basis, the study examined infant anthropometric measurements at birth, 1, 2 and 4 months of age. Women with a functional FUT2 have been found to have three strong HMOs present in their milk and it is these three HMOs that were studied in depth on a regular basis across the approximately 50 lactating mothers in the research group.

The mothers in the study were instructed to maintain a stable usual diet throughout the study, and the infants’ weight, height and head circumference were recorded at birth and at 1, 2 and 4 months. BMI was calculated. Breast milk samples were collected at 30, 60 and 120 days postpartum and carefully analysed. The study discovered that breast milk varies substantially both in HMO composition and amounts of specific oligosaccharide structures over the four months of lactation. The group was found to contain some mothers with high FUT2 status and some with low FUT2 concentrations, but this did not appear to have any major impact on infant growth parameters up to 4 months of age. Further study is required, but this initial new research concludes that FUT2 related alterations of breast milk HMOs composition as assessed through enzyme concentrations does not impact the growth of breastfed infants during the first 4 months of life.

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