Specific Human Milk Oligosaccharides Research Articles

Novel approach to visualize the inter-dependencies between maternal sensitization, breast milk immune components and human milk oligosaccharides in the LIFE Child cohort.

BackgroundNumerous studies have shown that specific components of breast milk, considered separately, are associated with disease status in the mother or the child using univariate analyses. However, very few studies have considered multivariate analysis approaches to evaluate the relationship between multiple breast milk components simultaneously.AimHere we aimed at visualizing breast milk component complex interactions in the context of the allergy status of the mother or the child.MethodsMilk samples were collected from lactating mothers participating in the Leipziger Forschungszentrum für Zivilisationskrankheiten (LIFE) Child cohort in Leipzig, Germany. A total of 156 breast milk samples, collected at 3 months after birth from mother/infant pairs, were analyzed for 51 breast milk components. Correlation, principal component analysis (PCA) and graphical discovery analysis were used.ResultCorrelations ranging from 0.40 to 0.96 were observed between breast milk fatty acid and breast milk phospholipids levels and correlations ranging from 0 to 0.76 between specific human milk oligosaccharides (HMO) were observed. No separation of the data based on the risk of allergy in the infants was identified using PCA. When graphical discovery analysis was used, dependencies between maternal plasma immunoglobulin E (IgE) level and the breast milk immune marker transforming growth factor-beta 2 (TGF-ß2), between TGF-ß2, breast milk immunoglobulin A (IgA) and TGF-ß1 as well as between breast milk total protein and birth weight were observed. Graphical discovery analysis also exemplifies a possible competition for the fucosyl group between 2’FL, LNFP-I and 3’FL in the HMO group. Additionally, dependencies between immune component IgA and specific HMO (6’SL and blood group A antigen tetraose type 5 or PI-HMO) were identified.ConclusionGraphical discovery analysis applied to complex matrices such as breast milk composition can aid in understanding the complexity of interactions between breast milk components and possible relations to health parameters in the mother or the infant. This approach can lead to novel discoveries in the context of health and diseases such as allergy. Our study thus represents the first attempt to visualize the complexity and the inter-dependency of breast milk components.

Factors affecting early-life intestinal microbiota development.

This paper reviews the published evidence on early-life intestinal microbiota development, as well as the different factors influencing its development before, at, and after birth. A literature search was done using PubMed, Cochrane and EMBASE databases. A growing body of evidence indicates that the intrauterine environment is not sterile as once presumed, but that maternal-fetal transmission of microbiota occurs during pregnancy. The consecutive order of bacteria with which the gastrointestinal tract is colonized will influence the outcome of community assembly and the ecological success of individual colonizers. The genetic background of the infant may also strongly influence microbial colonization of the gastrointestinal tract. The composition and development of infant gut microbiota can be influenced by many prenatal factors, such as maternal diet, obesity, smoking status, and use of antibiotic agents during pregnancy. Mode of delivery is generally accepted as a major factor determining the initial colonization. Breast milk stimulates the most balanced microbiome development for the infant, mainly because of its high content of unique oligosaccharides. Feeding is another important factor to determine intestinal colonization. Compared with breastfed infants, formula-fed infants have an increased richness of species. Initial clinical studies show that infant formulas supplemented with specific human milk oligosaccharides (HMOs) -2´-fucosyllactose alone or in combination with lacto-n-neotetraose are structurally identical to those in breast milk. HMOs increase the proportion of infants with a high bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants, lead to plasma immune marker profiles similar to those of breast-fed infants and to lower morbidity and antibiotics use. Further clinical studies with the same, others or more HMOs are needed to confirm these clinical effects. A growing number of studies have reported on how the composition and development of the microbiota during early life will affect risk factors related to health up to and during adulthood. If exclusive breastfeeding is not possible, the composition of infant formula should be adapted to stimulate the development of a bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants. The main components in breast milk that stimulate the growth of specific bifidobacteria are HMOs.

Neutral Human Milk Oligosaccharides Are Associated with Multiple Fixed and Modifiable Maternal and Infant Characteristics.

We aimed to identify if maternal and infant factors were associated with neutral human milk oligosaccharides (HMOs) variability and examined the associations between HMOs concentration and infant growth and disease status in healthy Chinese mothers over a 6-month lactation period. We recruited mothers and their full-term infants as our subjects. At 1–5 days, 8–14 days, 4 weeks, and 6 months postpartum, all participants were interviewed to collect breast milk samples, obtain follow-up data and measure infant length and weight at their local hospital. A total of 23 neutral HMOs were analyzed by high performance liquid chromatography (HPLC)- mass spectrometer (MS). Secretor and Lewis phenotype were determined by the concentration of 2′-fucosyllactose (2′-FL) and Lacto-N-fucopentaose (LNFP)-II. The associations between maternal and infant factors with HMOs concentrations were investigated. A total of 464 human breast milk samples were collected from 116 mothers at four different time points. In total, 76.7% mothers were found to be Secretor and Lewis positive phenotype (Se+Le+), 17.2% were Se-Le+, 4.3% were Se+Le-, and 1.7% were Se-Le-. Several individual HMOs, including 2′-FL, Lactodifucotetraose (LDFT), LNFP-I were determined by Secretor phenotype. Most individual HMOs decreased at the later stage of lactation, except 3′-FL. We suggest that Secretor phenotype and lactation stage could influence most of the neutral HMOs. Concentrations of specific HMOs may be associated with maternal age, allergic history, pre-pregnancy body mass index (BMI), parity, delivery mode, infant gestational age and gender.

Evidence of Human Milk Oligosaccharides in Cord Blood and Maternal-to-Fetal Transport across the Placenta.

Human milk oligosaccharides (HMOs) are present in maternal serum in early gestation, raising the question of whether HMOs can cross the placental barrier and reach fetal circulation. Here, we aimed to detect HMOs in cord blood, and assess HMO composition and concentration in relation to maternal HMOs. In an ex-vivo placental perfusion model, we asked whether HMOs can pass over the placenta. Using HPLC, we measured HMOs in maternal serum and matching venous cord blood samples collected at delivery from normal pregnancies (n = 22). To investigate maternal-to-fetal transport, we perfused isolated placental cotyledons from term pregnancies (n = 3) with 2’-fucosyllactose (2′FL) in a double closed setting. We found up to 18 oligosaccharides typically present in maternal serum in all cord serum samples investigated. Median total cord blood HMO concentration did not differ from the concentration in maternal serum. HMO composition resembled the composition in maternal serum, with the strongest correlations for 2′FL and LDFT. After 180 min perfusion, we found 22% of maternally offered 2′FL in the fetal circuit without reaching equilibrium. Our results provide direct evidence of HMOs in cord blood, and suggest that the placenta transfers HMOs from the maternal to fetal circuit. Future studies will investigate potential differences in the transfer of specific HMOs, or in pregnancy disorders.

Maternal and Infant Factors Associated with Human Milk Oligosaccharides Concentrations According to Secretor and Lewis Phenotypes.

Human milk oligosaccharides (HMOs) are multifunctional carbohydrates naturally present in human milk that act as prebiotics, prevent pathogen binding and infections, modulate the immune system and may support brain development in infants. HMOs composition is very individualized and differences in HMOs concentrations may affect the infant’s health. HMOs variability can be partially explained by the activity of Secretor (Se) and Lewis (Le) genes in the mother, but non-genetic maternal factors may also be involved. In this cross-sectional, observational study, 78 single human milk samples ranging from 17 to 76 days postpartum (median: 32 days, IQR: 25–46 days) were collected from breastfeeding Brazilian women, analyzed for 16 representative HMOs by liquid chromatography coupled to mass spectrometry and associations between maternal and infant factors with HMOs concentrations were investigated. HMOs concentrations presented a high variability even in women with the same SeLe phenotype and associations with maternal allergic disease, time postpartum and with infant’s weight, weight gain and sex. Overall, we present unprecedented data on HMOs concentrations from breastfeeding Brazilian women and novel associations of maternal allergic disease and infant’s sex with HMOs concentrations. Differences in HMOs composition attributed to maternal SeLe phenotype do not impact infant growth, but higher concentrations of specific HMOs may protect against excessive weight gain.

Correlating Infant Fecal Microbiota Composition and Human Milk Oligosaccharide Consumption by Microbiota of 1-Month-Old Breastfed Infants.

ScopeUnderstanding the biological functions of human milk oligosaccharides (HMOs) in shaping gastrointestinal (GI) tract microbiota during infancy is of great interest. A link between HMOs in maternal milk and infant fecal microbiota composition is examined and the role of microbiota in degrading HMOs within the GI tract of healthy, breastfed, 1‐month‐old infants is investigated.Methods and resultsMaternal breast milk and infant feces are from the KOALA Birth Cohort. HMOs are quantified in milk and infant fecal samples using liquid chromatography‐mass spectrometry. Fecal microbiota composition is characterized using Illumina HiSeq 16S rRNA gene amplicon sequencing. The composition is associated with gender, delivery mode, and milk HMOs: Lacto‐N‐fucopentaose I and 2′‐fucosyllactose. Overall, Bifidobacterium, Bacteroides, Escherichia–Shigella, and Parabacteroides are predominating genera. Three different patterns in infant fecal microbiota structure are detected. GI degradation of HMOs is strongly associated with fecal microbiota composition, and there is a link between utilization of specific HMOs and relative abundance of various phylotypes (operational taxonomic units).ConclusionsHMOs in maternal milk are among the important factors shaping GI tract microbiota in 1‐month‐old breastfed infants. An infant's ability to metabolize different HMOs strongly correlates with fecal microbiota composition and specifically with phylotypes within genera Bifidobacterium, Bacteroides, and Lactobacillus.

Human Milk Oligosaccharides: Factors Affecting Their Composition and Their Physiological Significance.

Human milk oligosaccharides (HMOs) are elongations of the milk sugar lactose by galactose, N-acetylglucosamine, fucose; and sialic acid. The HMO composition of breast milk is strongly influenced by polymorphisms of the maternal fucosyltransferases, FUT2 and FUT3, and by the stage of lactation. Clinical observational studies with breastfed infant-mother dyads associate specific HMOs with infant gut microbiota, morbidity, infectious diarrhea, and allergies. Observational and basic research data suggest that HMOs influence the establishment of early-life microbiota and mucosal immunity and inhibit pathogens, thereby contributing to protection from infections. Clinical intervention trials with infant formula supplemented with the single HMO, 2'-fucosyllactose (2'FL), or with 2 HMOs, 2'FL and lacto-N-neotetraose (LNnT), demonstrated that they allow for age-appropriate growth and are well tolerated. A priori defined exploratory outcomes related feeding an infant formula with 2 HMOs to fewer reported illnesses of the lower respiratory tract and reduced need for antibiotics during the first year of life compared to feeding a control formula. In parallel, early-life microbiota composition shifted towards that of breastfed infants. Together, HMOs likely contribute to immune protection in part through their effect on early-life gut microbiota, findings that warrant further clinical research to improve our understanding of HMO biology and significance for infant nutrition.

Human Milk Oligosaccharides in the Prevention of Necrotizing Enterocolitis: A Journey From in vitro and in vivo Models to Mother-Infant Cohort Studies.

Preterm infants who receive human milk instead of formula are 6- to 10-times less likely to develop necrotizing enterocolitis (NEC), one of the most common and devastating intestinal disorders that affects 5–10% of all very-low-birth-weight infants. Combined data from in vitro tissue culture models, in vivo preclinical studies in animal models, as well human mother-infant cohort studies support the hypothesis that human milk oligosaccharides (HMOs), complex sugars that are highly abundant in human milk but not in infant formula, contribute to the beneficial effects of human milk feeding in reducing NEC. The almost 20-year long journey of testing this hypothesis took an interesting turn during HMO in vivo efficacy testing and structure elucidation, suggesting that the original hypothesis may indeed be correct and specific HMO reduce NEC risk, however, the underlying mechanisms are likely different than originally postulated.

Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection

Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neonatal strain G10P[11], population studies show significantly higher levels of Lacto-N-tetraose (LNT), 2’-fucosyllactose (2’FL), and 6’-siallylactose (6’SL) in milk from mothers of rotavirus-positive neonates with gastrointestinal symptoms. Further, these HMOs correlate with abundance of Enterobacter/Klebsiella in maternal milk and infant stool. Specific HMOs also improve the infectivity of a neonatal strain-derived rotavirus vaccine. This study provides molecular and translational insight into host factors influencing neonatal rotavirus infections and identifies maternal components that could promote the performance of live, attenuated rotavirus vaccines.

Industrial Applications of Selected JFS Articles

Industrial Applications of Selected <i>JFS</i> Articles

Human milk glycomics and gut microbial genomics in infant feces show a correlation between human milk oligosaccharides and gut microbiota: a proof-of-concept study.

Human milk oligosaccharides (HMOs) play a key role in shaping and maintaining a healthy infant gut microbiota. This article demonstrates the potential of combining recent advances in glycomics and genomics to correlate abundances of fecal microbes and fecal HMOs. Serial fecal specimens from two healthy breast-fed infants were analyzed by bacterial DNA sequencing to characterize the microbiota and by mass spectrometry to determine abundances of specific HMOs that passed through the intestinal tract without being consumed by the luminal bacteria. In both infants, the fecal bacterial population shifted from non-HMO-consuming microbes to HMO-consuming bacteria during the first few weeks of life. An initial rise in fecal HMOs corresponded with bacterial populations composed primarily of non-HMO-consuming Enterobacteriaceae and Staphylococcaeae. This was followed by decreases in fecal HMOs as the proportion of HMO-consuming Bacteroidaceae and Bifidobacteriaceae increased. Analysis of HMO structures with isomer differentiation revealed that HMO consumption is highly structure-specific, with unique isomers being consumed and others passing through the gut unaltered. These results represent a proof-of-concept and are consistent with the highly selective, prebiotic effect of HMOs in shaping the gut microbiota in the first weeks of life. The analysis of selective fecal bacterial substrates as a measure of alterations in the gut microbiota may be a potential marker of dysbiosis.

Human Milk Oligosaccharides Influence Maturation of Human Intestinal Caco-2Bbe and HT-29 Cell Lines

Stimulation of gastrointestinal tract maturation is 1 of the many benefits of human milk. Human milk oligosaccharides (HMOs) are abundant in human milk and are reported to promote enterocyte differentiation in vitro. The objective of this study was to assess the impact of 3 predominant HMOs on multiple aspects of enterocyte maturation in vitro. Ranging from crypt-like to differentiated enterocytes, we used the well-characterized intestinal cell lines HT-29 and Caco-2Bbe to model early and late stages of differentiation, respectively. With this model of the crypt–villus axis made up of preconfluent HT-29, preconfluent Caco-2Bbe, and postconfluent Caco-2Bbe cultures, we characterized the impact of lacto-N-neotetraose (LNnT), 2′-fucosyllactose (2′FL), and 6′-sialyllactose on epithelial cell kinetics and function. All 3 HMOs dose-dependently inhibited cell proliferation in undifferentiated HT-29 and Caco-2Bbe cultures (P < 0.05). In contrast to previous reports, only treatment with 2′FL at concentrations similar to human milk increased alkaline phosphatase activity by 31% (P = 0.044) in HT-29 cultures and increased sucrase activity by 54% (P = 0.005) in well-differentiated Caco-2Bbe cultures. LNnT at concentrations similar to that reported for human milk increased transepithelial resistance by 21% (P = 0.002) in well-differentiated Caco-2Bbe cells. In summary, all 3 HMOs reduced cell proliferation in an epithelial cell model of the crypt–villus axis. However, effects on differentiation, digestive function, and epithelial barrier function differed between the HMOs tested. These results suggest differential roles for specific HMOs in maturation of the gastrointestinal tract.

Fucosylated but Not Sialylated Milk Oligosaccharides Diminish Colon Motor Contractions

Human milk oligosaccharides (HMO) are being studied by different groups exploring a broad range of potential beneficial effects to the breastfed infant. Many of these effects have been attributed to a growth promotion effect on certain gut organisms such as bifidobacteria. Additionally, evidence indicates that HMO are able to directly promote positive changes in gut epithelium and immune responses under certain conditions. This study utilizes a standardized ex vivo murine colon preparation to examine the effects of sialylated, fucosylated and other HMO on gut motor contractions. Only the fucosylated molecules, 2’FL and 3’FL, decreased contractility in a concentration dependent fashion. On the basis of IC50 determinations 3’FL was greater than 2 times more effective than 2’FL. The HMO 3’SL and 6’SL, lacto-N-neotetraose (LNnT), and galactooligosaccharides (GOS) elicited no effects. Lactose was used as a negative control. Fucosylation seems to underlie this functional regulation of gut contractility by oligosaccharides, and L-fucose, while it was also capable of reducing contractility, was substantially less effective than 3’FL and 2’FL. These results suggest that specific HMO are unlikely to be having these effects via bifidogenesis, but though direct action on neuronally dependent gut migrating motor complexes is likely and fucosylation is important in providing this function, we cannot conclusively shown that this is not indirectly mediated. Furthermore they support the possibility that fucosylated sugars and fucose might be useful as therapeutic or preventative adjuncts in disorders of gut motility, and possibly also have beneficial central nervous system effects.

Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes.

Human milk oligosaccharides (HMOS) are not digested in the proximal intestine. In distal intestine, HMOS collectively modify the microbiota, but the response of individual bacteria to individual components of the HMOS is not well defined. Here, each of 25 major isolates of the human intestinal microbiota was fed individual major fucosylated and sialylated HMOS in anaerobic culture. This allowed for an assessment of the influence of specific HMOS on the growth and metabolic products of individual microbiota bacteria. Most Bifidobacteria spp. and Bacteroides spp. grew, induced α-L-fucosidase activity, and produced abundant lactate or short-chain fatty acids (SCFAs) when fed 2'-fucosyllactose (2'-FL), 3-FL, and lactodifucotetraose (LDFT). Lactobacillus delbrueckii ATCC7830, Enterococcus faecalis ATCC19433, and Streptococcus thermophilus ATCC19258 exhibited slight growth, pH reduction, and lactate production when supplemented with 2'-FL or 3-FL, but not LDFT. Supplementation with 3'-sialyllactose (3'-SL) and 6'-SL promoted moderate growth of Bifidobacterium longum JCM7007, 7009, 7010, 7011, 1272, 11347, ATCC15708, Bacteroides vulgatus ATCC8482, and B. thetaiotaomicron ATCC29148; accordingly, these bacteria exhibited greater neuraminidase activity and produced copious lactate, SCFA, or both. Lactobacillus delbrueckii ATCC7830 also consumed 6'-SL. In contrast, Clostridium spp., L. rhamnosus ATCC53103, E. faecalis ATCC29200, Staphylococcus spp., Enterobacter spp., and Escherichia coli K12 did not consume milk oligosaccharides nor produce appreciable acidic fermentation products. Specific Bifidobacteria and Bacteroides differentially digest specific individual HMOS, with the major fucosylated milk oligosaccharides most strongly stimulating key species of mutualist symbionts. This suggests strategies for treating dysbiosis of the microbiota and associated inflammatory disorders.

Variation in Consumption of Human Milk Oligosaccharides by Infant Gut-Associated Strains of Bifidobacterium breve

Human milk contains a high concentration of complex oligosaccharides that influence the composition of the intestinal microbiota in breast-fed infants. Previous studies have indicated that select species such as Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum can utilize human milk oligosaccharides (HMO) in vitro as the sole carbon source, while the relatively few B. longum subsp. longum and Bifidobacterium breve isolates tested appear less adapted to these substrates. Considering the high frequency at which B. breve is isolated from breast-fed infant feces, we postulated that some B. breve strains can more vigorously consume HMO and thus are enriched in the breast-fed infant gastrointestinal tract. To examine this, a number of B. breve isolates from breast-fed infant feces were characterized for the presence of different glycosyl hydrolases that participate in HMO utilization, as well as by their ability to grow on HMO or specific HMO species such as lacto-N-tetraose (LNT) and fucosyllactose. All B. breve strains showed high levels of growth on LNT and lacto-N-neotetraose (LNnT), and, in general, growth on total HMO was moderate for most of the strains, with several strain differences. Growth and consumption of fucosylated HMO were strain dependent, mostly in isolates possessing a glycosyl hydrolase family 29 α-fucosidase. Glycoprofiling of the spent supernatant after HMO fermentation by select strains revealed that all B. breve strains can utilize sialylated HMO to a certain extent, especially sialyl-lacto-N-tetraose. Interestingly, this specific oligosaccharide was depleted before neutral LNT by strain SC95. In aggregate, this work indicates that the HMO consumption phenotype in B. breve is variable; however, some strains display specific adaptations to these substrates, enabling more vigorous consumption of fucosylated and sialylated HMO. These results provide a rationale for the predominance of this species in breast-fed infant feces and contribute to a more accurate picture of the ecology of the developing infant intestinal microbiota.

Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding

The inefficiency of HIV breast-milk transmission may be caused by the presence of immunologically active factors, including human milk oligosaccharides (HMOs). We investigated whether HMO concentrations are associated with a reduced risk of postnatal HIV transmission. A nested case-control study was conducted within a larger cohort study of HIV-infected women and their infants followed from birth to 24 mo in Lusaka, Zambia. Breast-milk samples collected at 1 mo from 81 HIV-infected women who transmitted via breastfeeding, a random sample of 86 HIV-infected women who did not transmit despite breastfeeding, and 36 uninfected breastfeeding women were selected. Total and specific HMO concentrations were measured by HPLC and compared between groups with adjustment for confounders by using logistic regression. HIV-infected women with total HMOs above the median (1.87 g/L) were less likely to transmit via breastfeeding (OR: 0.45; 95% CI: 0.21, 0.97; P = 0.04) after adjustment for CD4 count and breast-milk HIV RNA concentrations; a trend toward higher concentrations of lacto-N-neotetraose being associated with reduced transmission (OR: 0.49; 95% CI: 0.23, 1.04; P = 0.06) was also observed. The proportion of 3'-sialyllactose (3'-SL) per total HMOs was higher among transmitting than among nontransmitting women (P = 0.003) and correlated with higher plasma and breast-milk HIV RNA and lower CD4 counts. Neither Secretor nor Lewis status distinguished between transmitting and nontransmitting women. Higher concentrations of non-3'-SL HMOs were associated with protection against postnatal HIV transmission independent of other known risk factors. Further study of these novel, potentially anti-HIV components of breast milk is warranted.

Bacteroides in the Infant Gut Consume Milk Oligosaccharides via Mucus-Utilization Pathways

Newborns are colonized with an intestinal microbiota shortly after birth, but the factors governing the retention and abundance of specific microbial lineages are unknown. Nursing infants consume human milk oligosaccharides (HMOs) that pass undigested to the distal gut, where they may be digested by microbes. We determined that the prominent neonate gut residents, Bacteroides thetaiotaomicron and Bacteroides fragilis, induce the same genes during HMO consumption that are used to harvest host mucus glycans, which are structurally similar to HMOs. Lacto-N-neotetraose, a specific HMO component, selects for HMO-adapted species such as Bifidobacterium infantis, which cannot use mucus, and provides a selective advantage to B. infantis in vivo when biassociated with B. thetaiotaomicron in the gnotobiotic mouse gut. This indicates that the complex oligosaccharide mixture within HMOs attracts both mutualistic mucus-adapted species and HMO-adapted bifidobacteria to the infant intestine that likely facilitate both milk and future solid food digestion.

Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation.

Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase high-performance liquid chromatography. The resultant oligosaccharide peaks, identified by co-elution with authentic standards and mass spectrometry, ranged in size from tri- to octasaccharides. The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation.

Oligosaccharides in Human Milk and Bacterial Colonization

Oligosaccharides in Human Milk and Bacterial Colonization