Associations between human milk oligosaccharides and growth in infancy and early childhood.
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SUBMITTER: Lagstrom H
PROVIDER: S-EPMC7138667 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundWe aimed to estimate associations between human milk oligosaccharides (HMOs) and infant growth (length-for-age (LAZ) and weight-for-length (WLZ) z-scores) at 12 months postnatal age.MethodsIn this secondary analysis of data from a maternal vitamin D trial in Dhaka, Bangladesh (N = 192), absolute concentrations of HMOs were measured in 13 ± 1 week(s) postpartum milk samples, infant anthropometric measurements were obtained soon after birth and at 12 months postpartum, and infant feeding was classified during 6 months postpartum. Associations between individual HMOs or HMO groups and LAZ or WLZ were estimated by multivariable linear regression adjusting for infant feeding pattern, maternal secretor status, and other potential confounders.ResultsThe concentrations of 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated HMOs were inversely associated with LAZ at 12 months of age, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months. These associations were robust in analyses restricted to infants who were primarily exclusively/predominantly fed human milk during the first 3 (or 6) months.ConclusionsSince HMOs are both positively and negatively associated with postnatal growth, there is a need for randomized trials to estimate the causal benefits and risks of exogenously administered HMOs on infant growth and other health outcomes.Impact6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated human milk oligosaccharides (HMOs) were inversely associated with length-for-age z-scores (LAZ) at 12 months, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months among Bangladeshi infants. Associations between individual and grouped HMOs with infant length growth at 12 months were as strong or stronger in analyses restricted to infants who were exclusively or predominantly fed human milk up to 3 (or 6) months. Randomized trials are needed to characterize the effects of specific HMOs on infant growth, particularly in countries where postnatal linear growth faltering is common.
| S-EPMC11343707 | biostudies-literature
Project description:Complex sugars found in breastmilk, human milk oligosaccharides (HMOs), may assist in early-life immune programming and prevention against infectious diseases. This study aimed to systematically review the associations between maternal levels of HMOs and development of immune-mediated or infectious diseases in the offspring. PubMed and EMBASE databases were searched (last search on 22 February 2018) according to a predetermined search strategy. Original studies published in English examining the effect of HMOs on immune-mediated and infectious disease were eligible for inclusion. Of 847 identified records, 10 articles from 6 original studies were included, with study quality ranging from low to high. Of three studies to examine allergic disease outcomes, one reported a protective effect against cow's milk allergy (CMA) by 18 months of age associated with lower lacto-N-fucopentaose (LNFP) III concentrations (OR: 6.7, 95% CI 2.0-22). Another study found higher relative abundance of fucosyloligosaccharides was associated with reduced diarrhea incidence by 2 years, due to (i) stable toxin-E. coli infection (p = 0.04) and (ii) "all causes" (p = 0.042). Higher LNFP-II concentrations were associated with (i) reduced cases of gastroenteritis and respiratory tract infections at 6 weeks (p = 0.004, p = 0.010) and 12 weeks (p = 0.038, p = 0.038) and (ii) reduced HIV transmission (OR: 0.45; 95% CI: 0.21-0.97) and mortality risk among HIV-exposed, uninfected infants (HR: 0.33; 95% CI: 0.14-0.74) by 24 months. Due to heterogeneity of the outcomes reported, pooling of results was not possible. There was limited evidence that low concentrations of LNFP-III are associated with CMA and that higher fucosyloligosaccharide levels protect infants against infectious disease. Further research is needed.
| S-EPMC5920034 | biostudies-literature
Project description:Human milk oligosaccharides (HMO), which constitute a major component of human milk, promote the growth of particular bacterial species in the infant's gastrointestinal tract. We hypothesized that HMO also interact with the bacterial communities present in human milk. To test this hypothesis, two experiments were conducted. First, milk samples were collected from healthy women (n = 16); culture-independent analysis of the bacterial communities was performed, HMO content was analyzed, and the relation between these factors was investigated. A positive correlation was observed between the relative abundance of Staphylococcus and total HMO content (r = 0.66). In a follow-up study, we conducted a series of in vitro growth curve experiments utilizing Staphylococcus aureus or Staphylococcus epidermidis and HMO isolated from human milk. HMO exhibited stimulatory effects on bacterial growth under various nutritional conditions. Analysis of culture supernatants from these experiments revealed that HMO did not measurably disappear from the culture medium, indicating that the growth-enhancing effects were not a result of bacterial metabolism of the HMO. Instead, stimulation of growth caused greater utilization of amino acids in minimal medium. Collectively, the data provide evidence that HMO may promote the growth of Staphylococcus species in the lactating mammary gland.
| S-EPMC3416375 | biostudies-literature
Project description:Several studies have reported associations between appetitive traits and weight gain during infancy or childhood, but none have directly compared these associations across both age periods. Here, we tested the associations between appetitive traits and growth velocities from birth to childhood. Appetitive trait data were collected using the Children's Eating Behaviour Questionnaire (CEBQ) in 149 children from the Cambridge Baby Growth Study at age 9-17 years. These participants also provided anthropometric measurements during infancy (birth, 3, 12, 18, and 24 months) and childhood (5 to 11 years). Standardized growth velocities (in weight, length/height, BMI, and body fat percentage) for 0-3 months, 3-24 months, and 24 months to childhood were estimated using individual linear-spline models. Associations between each of the eight CEBQ traits and each growth velocity were tested in separate multilevel linear regression models, adjusted for sex, age at CEBQ completion, and the corresponding birth measurement (weight, length, BMI, or body fat percentage). The three food-approach traits (food responsiveness, enjoyment of food and emotional overeating) were positively associated with infancy and childhood growth velocities in weight, BMI, and body fat percentage. By contrast, only one of the food-avoidant traits, satiety responsiveness, was negatively associated with all growth velocities. Significant associations were mostly of similar magnitude across all age periods. These findings reveal a broadly consistent relationship between appetitive traits with gains in weight and adiposity throughout infancy and childhood. Future interventions and strategies to prevent obesity may benefit from measuring appetitive traits in infants and children and targeting these as part of their programs.
| S-EPMC10520028 | biostudies-literature
Project description:BackgroundThe relationship between human milk oligosaccharides (HMO) and child growth has been investigated only insufficiently with ambiguous results. Therefore, this study examines potential influencing factors of HMO concentrations and how HMO are associated with child growth parameters.MethodsMilk samples from the German LIFE Child cohort of healthy children were analyzed for 9 HMO. Putative associations with maternal and child cofactors and child height, head circumference and BMI between 3 months and 7 years of age were examined. Secretor status, defined as the presence of 2'-fucosyllactose, was investigated for associations with infant outcomes.ResultsOur population consisted of 21 (14.7%) non-secretor and 122 (85.3%) secretor mothers. Maternal age was significantly associated with higher 3'SL concentrations; gestational age was associated with LNT, 6'SL and LNFP-I. Pre-pregnancy BMI was negatively associated with LNnT only in non-secretors. The growth velocity of non-secretors' children was inversely associated with LNnT at 3 months to 1 year (R = 0.95 [0.90, 0.99], p = 0.014), 1 to 2 years (R = 0.80 [0.72, 0.88], p < 0.001) and 5 to 6 years (R = 0.71 [0.57, 0.87], p = 0.002). 2'FL was negatively associated with BMI consistently, reaching statistical significance at 3 months and 4 and 5 years. Children of non-secretors showed higher BMI at 3 months, 6 months, and 3, 6, and 7 years of age.ConclusionWe found that some associations between HMO and infant growth may extend beyond the infancy and breastfeeding periods. They highlight the importance of both maternal and infant parameters in the understanding of the underlying associations.Trial registrationThe study is registered with ClinicalTrial.gov: NCT02550236 .
| S-EPMC8556924 | biostudies-literature
Project description:BackgroundEvidence linking breastfeeding to reduced risk of developing childhood obesity is inconclusive, yet previous studies have not considered variation in specific components of breast milk that may affect early development.ObjectiveWe examined whether differences in the composition of human milk oligosaccharides (HMOs) correlate with infant growth and body composition at 1 and 6 mo of age.DesignTwenty-five mother-infant dyads were recruited from the University Hospital at the University of Oklahoma Health Sciences Center. Infants were breastfed for 6 mo. Breast-milk and infant measures were obtained at 1 and 6 mo of infant age. HMO composition was analyzed by high-pressure liquid chromatography, and infant growth (length and weight) and body composition (percentage fat, total fat, lean mass) were measured by dual-energy X-ray absorptiometry. Relations between HMOs and infant growth and body composition were examined by using multiple linear regression. A priori covariates included maternal prepregnancy body mass index, pregnancy weight gain, and infant age and sex.ResultsHigher HMO diversity and evenness at 1 mo were associated with lower total and percentage fat mass at 1 mo. At 1 mo, each 1-μg/mL increase in lacto-N-fucopentaose (LNFP) I was associated with a 0.40-kg lower infant weight (P = 0.03). At 6 mo, each 1-μg/mL increase in LNFPI was associated with a 1.11-kg lower weight (P = 0.03) and a 0.85-g lower lean mass (P = 0.01). At 6 mo, each 1-μg/mL increase in LNFPI was associated with a 0.79-g lower fat mass (P = 0.02), whereas disialyl-lacto-N-tetraose and LNFPII were associated with a 1.92-g (P = 0.02) and 0.42-g (P = 0.02) greater fat mass, respectively. At 6 mo, each 1-μg/mL increase in fucosyl-disialyl-lacto-N-hexaose and lacto-N-neotetraose was associated with 0.04% higher (P = 0.03) and 0.03% lower (P < 0.01) body fat, respectively.ConclusionThese findings support the hypothesis that differences in HMO composition in mother's milk are associated with infant growth and body composition. This trial was registered at clinicaltrials.gov as NCT02535637.
| S-EPMC6546222 | biostudies-literature
Project description:BackgroundHuman milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries.ObjectivesWe aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi.MethodsBreast milk samples were analyzed at 6 mo (n = 659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing.ResultsAmong all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (P = 0.018 and P = 0.044), and a positive association of lactalbumin concentration with motor skills (P = 0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (P = 0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (P < 0.001 and P = 0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (P = 0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors.ConclusionsCertain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists.This trial was registered at clinicaltrials.gov as NCT01239693.
| S-EPMC7779225 | biostudies-literature
Project description:Despite the significant role of the gut microbiota in infant health and development, little is known about the ecological processes determining gut microbial community assembly. According to ecology theory, the timing and order of arrival of microbial species into an ecosystem affect microbial community assembly, a phenomenon termed priority effects. Bifidobacterium species are recognized as highly abundant early colonizers of the infant's gut, partly due to their ability to selectively utilize human milk oligosaccharides (HMOs) from breast milk. However, the role of priority effects in Bifidobacterium community assembly remains unclear. Here, we investigated the Bifidobacterium community assembly in the gut of 25 breastfed Danish infants longitudinally sampled throughout the first 6 months of life. Our results showed that the breastfed infants were often initially, but temporarily, dominated by suboptimal HMO-utilizing Bifidobacterium taxa, such as B. longum subsp. longum, before more efficient HMO-utilizers such as B. longum subsp. infantis, replaced the first colonizer as the dominant Bifidobacterium taxon. Subsequently, we validated this observation using gnotobiotic mice sequentially colonized with B. longum subsp. longum and B. longum subsp. infantis or vice versa, with or without supplementation of HMOs in the drinking water. The results showed that in the absence of HMOs, order of arrival determined dominance. Yet, when mice were supplemented with HMOs the strength of priority effects diminished, and B. longum subsp. infantis dominated regardless of colonization order. Our data demonstrate that the arrival order of Bifidobacterium taxa and the deterministic force of breast milk-derived HMOs, dictate Bifidobacterium community assembly in the infant's gut.
| S-EPMC10689826 | biostudies-literature
Project description:It was previously observed that maternal iron supplementation in pregnancy was associated with increased offspring size and adiposity at birth, possibly mediated through increased risk of gestational diabetes. In this study we investigated potential long-term associations of maternal iron supplementation in pregnancy with offspring growth in infancy, and growth and cardiometabolic risk factors in mid-childhood to seek evidence of nutritional programming. Using a nested case-control format, markers of growth and adiposity were measured at 3, 12 and 24 months of age in 341 infants from the Cambridge Baby Growth Study whose mothers supplemented with iron in pregnancy and 222 infants whose mothers did not. Measures of growth, glucose tolerance (using a 30 minute 1.75 g glucose/kg body weight oral glucose tolerance test), insulin sensitivity (HOMA IR) and blood pressure were collected in 122 and 79 of these children, respectively, at around 9.5 years of age. In infancy adiposity-promoting associations with maternal iron supplementation in pregnancy were evident at 3 months of age (e.g. mean difference in skinfold thickness: β = +0.15 mm, p = 0.02, in n = 341 whose mothers supplemented versus 222 that did not; waist circumference: β = +0.7 cm, p = 0.04, in n = 159 and 78, respectively) but differences lessened after this time (e.g. 3-12 month change in mean difference in skinfold thickness: β = -0.2 mm, p = 0.03, in n = 272 and 178, respectively). At ~9.5 years of age children whose mothers supplemented with iron in pregnancy had lower mean arterial blood pressures (β = -1.0 mmHg, p = 0.03, in n = 119 and 78, respectively). There were no apparent differences in markers of growth or other cardiometabolic factors. These results suggest that most of the associations of maternal iron supplementation in pregnancy on growth and adiposity evident at birth disappear during infancy, but there may be some evidence of long-term nutritional programming of blood pressure in mid-childhood.
| S-EPMC9140278 | biostudies-literature
Project description:Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of invasive bacterial infections in newborns, typically acquired vertically during childbirth secondary to maternal vaginal colonization. Human milk oligosaccharides (HMOs) have important nutritional and biological activities that guide the development of the immune system of the infant and shape the composition of normal gut microbiota. In this manner, HMOs help protect against pathogen colonization and reduce the risk of infection. In the course of our studies of HMO-microbial interactions, we unexpectedly uncovered a novel HMO property to directly inhibit the growth of GBS independent of host immunity. By separating different HMO fractions through multidimensional chromatography, we found the bacteriostatic activity to be confined to specific non-sialylated HMOs and synergistic with a number of conventional antibiotic agents. Phenotypic screening of a GBS transposon insertion library identified a mutation within a GBS-specific gene encoding a putative glycosyltransferase that confers resistance to HMOs, suggesting that HMOs may function as an alternative substrate to modify a GBS component in a manner that impairs growth kinetics. Our study uncovers a unique antibacterial role for HMOs against a leading neonatal pathogen and expands the potential therapeutic utility of these versatile molecules.
| S-EPMC5500792 | biostudies-literature