Dataset Information

Structure-Specific and Individual-Dependent Metabolization of Human Milk Oligosaccharides in Infants: A Longitudinal Birth Cohort Study.

ABSTRACT: To follow human milk oligosaccharide (HMO) biosynthesis and in vivometabolization, mother milk and infant feces from 68 mother-infant dyads at 2, 6, and 12 weeks postpartum were analyzed, with 18 major HMOs quantitated. Fucosylated and neutral core HMO levels in milk were dependent on mothers' Lewis/Secretor status, whereas most sialylated HMO levels were independent. Infant fecal excretion of HMOs gradually declined with age, especially for neutral core structures. Although decreasing in absolute concentrations in milk during lactation, the relative abundance of total fucosylated HMOs increased in both milk and feces. Mono-fucosylated HMOs were more consumed than those decorated with two fucose moieties. More (α2-3)-sialylated HMOs were degraded than (α2-6)-sialylated HMOs. The transition speed of HMO metabolization from nonspecific or structure-specific consumption stage to the complete consumption stage was individual-dependent. Variation was associated with mode and place of delivery, where caesarean section or early exposure to hospital environment delayed the transition.

SUBMITTER: Gu F

PROVIDER: S-EPMC8193636 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Structure-Specific and Individual-Dependent Metabolization of Human Milk Oligosaccharides in Infants: A Longitudinal Birth Cohort Study.

Gu Fangjie F Wang Shuang S Beijers Roseriet R de Weerth Carolina C Schols Henk A HA

Journal of agricultural and food chemistry 20210525 22

To follow human milk oligosaccharide (HMO) biosynthesis and in vivometabolization, mother milk and infant feces from 68 mother-infant dyads at 2, 6, and 12 weeks postpartum were analyzed, with 18 major HMOs quantitated. Fucosylated and neutral core HMO levels in milk were dependent on mothers' Lewis/Secretor status, whereas most sialylated HMO levels were independent. Infant fecal excretion of HMOs gradually declined with age, especially for neutral core structures. Although decreasing in absolu ...[more]

PMID: 34032401

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Project description:BackgroundHuman milk is the recommended and sole nutrient source for newborns. One of the largest components of human milk is oligosaccharides (HMOs) with major constituents determined by the mother genotype for the fucosyltransferase 2 (FUT2, secretor) gene. HMO variation has been related with infant microbiota establishment, diarrhea incidence, morbidity and mortality, IgE associated eczema and body composition.ObjectivesWe investigated the (i) dependence of several major representative HMOs on the FUT2 status assessed through breast milk 2'Fucosyllactose (2'FL) and (ii) the relation of the 2'FL status with infant growth up to 4 months of life.DesignFrom an open observatory, single center, longitudinal cohort study with quantitative human milk collection at 30, 60, and 120 days postpartum from 50 mothers, who gave birth to 25 female and 25 male singleton infants, we collected a representative sample of human milk. We quantified the following 5 representative HMOs: 2'FL, Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL) and 6'Sialyllactose (6'SL). We grouped the milk samples and corresponding infants according to the measured milk 2'FL concentrations at 30 days of lactation, which clustered around low concentrations (95% CI of mean 12-42 mg/L) and high concentrations (95% CI of mean 1880-2460 mg/L) with the former likely representing Secretor negative mothers. Infant anthropometric measures were recorded at birth, 1, 2 and 4 months of age. Relations among the quantified HMOs and the relation of the high and low 2'FL HMOs groups with infant growth parameters were investigated via linear mixed models.ResultsThe milk samples with low 2'FL concentration had higher LNT and lower LNnT concentrations compared to the samples with high 2'FL. The milk 3'- and 6'SL concentrations were independent of 2'FL. Over lactation time we observed a drop in the concentration of 2'FL, LNT, LNnT and 6'SL, especially from 1 to 2 months, while 3'SL remained at relatively constant concentration from 1 month onwards. Up to 4 months of age, we did not observe significant differences in body weight, body length, body mass index and head circumference of the infants who consumed breast milk with low or high FUT2 associated HMO concentrations and composition.ConclusionsOur findings on HMO concentrations over time of lactation and clusters based on 2'FL concentrations confirm previous observations and suggest that LNnT and LNT are 'co-regulated' with the FUT2 dependent 2'FL concentration, with LNnT showing a positive and LNT a negative relation. Further, our findings also suggest that the relatively substantial variation in HMOs between the high and low 2'FL clusters do not impact infant growth of either sex up to 4 months of age. The study was registered in www.ClinicalTrial.gov (NCT01805011).

Project description:BackgroundOligosaccharides are the third most abundant component in human milk. They are a potential protective agent against neonatal sepsis.ObjectivesWe aimed to explore the association between human milk oligosaccharides (HMOs) and late-onset sepsis in very-low-birth-weight infants, and to describe the composition and characteristics of HMOs in Peruvian mothers of these infants.MethodsThis is a secondary data analysis of a randomized clinical trial. We conducted a retrospective cohort study of mothers and their very-low-birth-weight (<1500 g) infants with ≥1 milk sample and follow-up data for >30 d. HMOs were measured by high performance liquid chromatography (HPLC). We used factor analysis and the Mantel-Cox test to explore the association between HMOs and late-onset neonatal sepsis.ResultsWe included 153 mother-infant pairs and 208 milk samples. Overall, the frequency of the secretor phenotype was 93%. Secretors and nonsecretors were defined by the presence and near-absence of α1-2-fucosylated HMOs, respectively. The most abundant oligosaccharides were 2'-fucosyllactose, lacto-N-fucopentaose (LNFP) I, and difucosyllacto-N-tetraose in secretors and lacto-N-tetraose and LNFP II in nonsecretors. Secretors had higher amounts of total oligosaccharides than nonsecretors (11.45 g/L; IQR: 0.773 g/L compared with 8.04 g/L; IQR: 0.449 g/L). Mature milk samples were more diverse in terms of HMOs than colostrum (Simpson's Reciprocal Diversity Index). We found an association of factor 3 in colostrum with a reduced risk of late-onset sepsis (HR: 0.63; 95% CI: 0.41, 0.97). Fucosyl-disialyllacto-N-hexose (FDSLNH) was the only oligosaccharide correlated to factor 3.ConclusionsThese findings suggest that concentrations of different HMOs vary from one individual to another according to their lactation period and secretor status. We also found that FDSLNH might protect infants with very low birth weight from late-onset neonatal sepsis. Confirming this association could prove 1 more mechanism by which human milk protects infants against infections and open the door to clinical applications of HMOs.This trial was registered at clinicaltrials.gov as NCT01525316.

Project description:Preterm birth (PTB) is one of the leading causes of neonatal mortality. The causes for spontaneous PTB are multifactorial and often remain unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with or without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood. We identified several microbial signatures, such as Lactobacillus jensenii, L. gasseri, Ureaplasma sp., and Gardnerella sp., associated with a short cervix, PTB, and/or preterm contractions. In addition, we observed associations between sialylated HMOs, in particular 3'-sialyllactose, with PTB, short cervix, and increased inflammation and confirmed an influence of HMOs on the microbiome profile. Since they identify serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum. Another process might be microbiome mediated and potentially associated with specific HMO signatures in urine. Our results support current efforts to improve diagnostics and therapeutic strategies in PTB.IMPORTANCE The causes for preterm birth (PTB) often remain elusive. We investigated whether circulating human milk oligosaccharides (HMOs) might be involved in modulating urinary and vaginal microbiome promoting or preventing PTB. We identified here HMOs and key microbial taxa associated with indicators of PTB. Based on our results, we propose two models for how HMOs might modulate risk for PTB: (i) by changes in HMOs associated with sterile inflammation (microbiome-independent) and (ii) by HMO-driven shifts in microbiome (microbiome-dependent). Our findings will guide current efforts to better predict the risk for PTB in seemingly healthy pregnant women and also provide appropriate preventive strategies.

Project description:PurposeThe Japanese Human Milk Study, a longitudinal prospective cohort study, was set up to clarify how maternal health, nutritional status, lifestyle and sociodemographic and economic factors affect breastfeeding practices and human milk composition. This would eventually determine factors affecting the growth and development of infants and children.ParticipantsA total of 1210 Japanese lactating women who satisfied the inclusion criteria, were invited across the country at various participating sites, between 2014 and 2019. Finally a total of 1122 women were enrolled in this study.Findings to dateAmong 1122 eligible participants, mean age at delivery was 31.2 (SD 4.4) years and mean prepregnancy BMI was 20.8 (SD 2.7). Among these women, 35% were previously nulliparous and 77.7% had college, university or higher education. The mean gestational period was 39.0 (SD 1.3) weeks. Caesarean section was reported among 11.9%; mean infant birth weight was 3082 (SD 360) g. Of the infants, 53.7% were male. Overall, our participants appeared to be healthier than the general population in Japan. Analyses of the 1079 eligible human milk samples obtained at the first and second months postpartum showed the following composition: carbohydrate, 8.13 (SD 0.32) g/100 mL; fat, 3.77 (SD 1.29) g/100 mL; and crude protein, 1.20 (SD 0.23) g/100 mL. We also analysed osteopontin, fatty acid, vitamin D and phospholipid levels in limited subcohorts of the samples.Future plansFollow-up surveys will be conducted to obtain milk samples every 2 months for 12 months and to investigate mother and child health until the children reach 5 years of age. These will be completed in 2024. We plan to longitudinally analyse the composition of macronutrients and various bioactive factors in human milk and investigate the lifestyle and environmental factors that influence breastfeeding practices, maternal and child health, and child development.Trial registration numberUMIN000015494; pre-results.

Project description:Background and aimHuman milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants.MethodsThis retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables.ResultsOf 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979).ConclusionsA daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants.Trial registrationClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.

Dataset Information

Structure-Specific and Individual-Dependent Metabolization of Human Milk Oligosaccharides in Infants: A Longitudinal Birth Cohort Study.

Publications

Structure-Specific and Individual-Dependent Metabolization of Human Milk Oligosaccharides in Infants: A Longitudinal Birth Cohort Study.

Similar Datasets

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