Human Milk Oligosaccharide Compositions Illustrate Global Variations in Early Nutrition

Abstract

Background Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant and specifically the brain, immune system, and gut microbiome. Objectives Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semi-rural and rural sites across geographically diverse countries. Methods Liquid chromatography mass spectrometry-based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant's sex, and residing geographical locations. Results A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately month six postnatal, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed, instead milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors (mothers with relatively high concentrations α(1,2)-fucosylated structures) in their populations compared to the rest of the globe, with Bolivia∼ 100%, Peru ∼97%, Brazil∼ 90%, and Argentina∼ 85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, The Gambia∼ 64%, and Malawi∼75%). Furthermore, we compared total abundance of HMOs in secretors versus non-secretors and found that non secretors have lower abundances of HMOs compared to secretors regardless of geographical location. We also observed compositional differences of the 50 + most abundant HMOs between milk types and geographical locations. Conclusion This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.

Human milk nutritional composition across lactational stages in Central Africa

“…Precisely, a high index of food insecurity was associated with lower levels of fatty-acids, amino acids, retinol, and the majority of the HMO measured in HM. This is in agreement with the results found by Vinjamuri et al ( 48 ), who found that HM from mothers living in countries with a low GDP per capita had lower HMO levels in 2,000 HM samples from over 1,000 mothers in geographically diverse countries.…”

“…As found in other HM cohort analyses, total HMO levels decreased significantly during the first 6 months of lactation (48,49,56,64,(75)(76)(77). 3-FL was the only HMO found to significantly increase during the first 6 month after birth, which is in line with findings in European and Asian HM cohorts (39,66,67,75).…”

“…While the preponderance of HM-type III among Central-African women is rare, the rate of Secretor + women is similar to the ones found in Kenya (72%) (47) or Malawi, and slightly higher than the ones found in South Africa or the Gambia (48). A review including 57 peer-reviewed articles gathering evidence from 31 countries worldwide reported that 70% of the women of these studies displayed the HM-type I phenotype, 20% the HM-type II phenotype, 9% the HM-type III phenotype, and 1% the HM-type IV phenotype (49).…”

Milk: A Scientific Model for Diet and Health Research in the 21st Century

“…The diversity of lactation across mammalia is an important asset, so the goal of the IMGC was to assemble a variety of entire genomes from marsupials to humans (6). Comparing these genomes formed the basis for interpreting the evolution of mammalian lactation (7), the expression of genes during lactation (8), the sequences (9) and digestibility of proteins (10), the sequences of peptides (11) and their formation (12), the biosynthetic pathways of glycans ( 13), the variation among women due to genetic diversity (14), timing of lactation (15), diet ( 16) and the biosynthesis of lipids (17).…”

“…Glycan structures are both free and bonded to proteins, peptides or lipids again by enzymatic synthesis. Every glycan, in each sample, must be explicitly analyzed to be identified (14).…”