Systematic Characterization and Longitudinal Study Reveal Distinguishing Features of Human Milk Oligosaccharides in China

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Human milk oligosaccharides (HMOs) in breast milk contribute to the development of neonatal microbiota and immune system. However, longitudinal studies examining HMOs profiles of Chinese mothers remain scarce.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>To analyze HMOs profiles including their composition, concentrations, and changes during lactation in milk of Chinese mothers.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A total of 822 milk samples from 222 mothers were collected, of which 163 mothers provided single samples. Samples from remaining 59 mothers were collected on day3, day7 and thereafter every 7 or 14 days until day168. 24 HMOs were studied using high-performance anion-exchange chromatography (HPAEC). Secretor and non-secretor status were determined based on Lewis blood types and a defined 2’-Fucosyllactose (2’-FL) threshold.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>77% of the 222 mothers were secretors and 23% were non-secretors. Longitudinal study involving 59 mothers showed that the total HMOs in secretors were significantly greater than those in non-secretors during the first two weeks. Acidic HMOs decreased significantly during lactation and were similar between secretors and non-secretors. Among neutral HMOs, distinctive differences were observed. Non-fucosylated and α-1–3/4-fucosylated HMOs in non-secretors were significantly higher than those in secretors during the first month. In contrast, α-1–2-fucosylated HMOs in secretors were significantly higher than those in non-secretors throughout 168 days. In secretors, 2'-FL levels peaked at 3.02 ± 0.14 g/L (day3) followed by significant decreases. In non-secretors, 2'-FL levels were fairly low throughout 168 days. Of the 24 studied HMOs, only 3-Fucosyllactose (3-FL) levels increased during lactation in both secretor and non-secretor mothers.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our study showed dynamic changes of 24 HMOs in secretors and non-secretors during lactation and revealed unique features of these HMOs profiles in the milk of Chinese mothers. Interestingly, 2'-FL levels in secretors were found to be lower than those of western populations but higher than those of African populations.</jats:p> </jats:sec>

Clinical Evaluation of 16-Week Supplementation with 5HMO-Mix in Healthy-Term Human Infants to Determine Tolerability, Safety, and Effect on Growth

“…The HMO intake ranged from 2.6 ± 0.79 g/day at V1 to 5.2 ± 0.7 g/day at V6, showing only a slight increase after 4 weeks. The total HMO concentration and the ratio of the HMOs in the formula remained constant during the intervention period, whereas in breast milk the concentration of several HMOs decreases within the first few months after delivery [ 40 ], while a few HMOs, such as 3-FL, become more abundant [ 29 , 40 ]. The absolute concentration of different HMOs is primarily influenced by the mother’s Secretor status but also by her BMI and diet as well as several other factors described above [ 40 , 61 ].…”

“…The total HMO concentration and the ratio of the HMOs in the formula remained constant during the intervention period, whereas in breast milk the concentration of several HMOs decreases within the first few months after delivery [ 40 ], while a few HMOs, such as 3-FL, become more abundant [ 29 , 40 ]. The absolute concentration of different HMOs is primarily influenced by the mother’s Secretor status but also by her BMI and diet as well as several other factors described above [ 40 , 61 ]. The overall concentration of HMOs declines from 20–25 g/L in the colostrum to 10–15 g/L in mature milk ([ 33 , 34 ] and references therein).…”

“…Among the nonfucosylated neutral HMOs, lacto- N -tetraose (LNT) is the most abundant, with a concentration range of 0.2–1.7 g/L. These data were compiled by comparing reported HMO concentrations explored in longitudinal studies that analyzed breast milk of mothers that delivered term infants [ 29 , 34 , 36 , 38 , 39 , 40 , 41 ]. To provide infant formulae that match the HMO profile of natural breast milk as closely as possible, we developed a mixture of five HMOs (5HMO-Mix) that combines the five most abundant HMOs across all three structural classes, aiming for synergistical and complementary beneficial effects for the infant’s development.…”

Human Milk Oligosaccharides: Their Effects on the Host and Their Potential as Therapeutic Agents

“…The composition of HMOs in human milk is also dependent on genetic factors, including secretor and Lewis blood status of women ( Table 1 ) ( 21 , 22 ). The secretor gene ( Se ) encodes an α1-2-fucosyltransferase (FUT2), and the Lewis gene ( Le ) encodes an α1-3/4-fucosyltransferase (FUT3), allowing the fucosylation of HMOs.…”

In Love with Shaping You—Influential Factors on the Breast Milk Content of Human Milk Oligosaccharides and Their Decisive Roles for Neonatal Development

“…Obviously, the analysis of the absolute HMO content does not give detailed information about the change of individual HMOs with regard to different factors. To address such questions, a good number of studies have therefore focused on the quantification of the most important milk sugars [ 7 , 12 , 17 , 20 , 28 , 29 , 42 , 43 , 46 , 47 , 48 ]. These have for instance shown that 3FL increases up to almost threefold throughout the course of lactation regardless of the milk status and gestational age [ 7 , 12 , 17 , 28 , 29 , 32 , 43 , 47 , 48 ].…”