Associations between human milk oligosaccharides and growth in infancy and early childhood

Lagström, Hanna; Rautava, Samuli; Ollila, Helena; Kaljonen, Anne; Turta, Olli; Mäkelä, Johanna; Yonemitsu, Chloe; Gupta, Julia; Bode, Lars

doi:10.1093/ajcn/nqaa010

Cited by 89 publications

(145 citation statements)

References 32 publications

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“…Overall, although the variation in BMI and weight z-scores in the present population was generally small with values proximal to zero, IGF-1, and cGP displayed significant associations with infant growth outcomes. This, together with evidence arising from other studies in the same cohort ( 62 ), suggests a role for HM-borne compounds in contributing to postnatal growth trajectories. As the role of IGF-1 in association with adiposity in infancy remains poorly understood and current data remain conflicting, more comprehensive studies are required to investigate the mechanistic role of IGF-1 and cGP in HM and early development.…”

Section: Discussionsupporting

confidence: 66%

Growth Factor Concentrations in Human Milk Are Associated With Infant Weight and BMI From Birth to 5 Years

et al. 2020

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Background: Human milk bioactives may play a role in infant health and development. Although the variability in their concentrations in milk is well-established, the impact of differential milk profiles on infant growth outcomes remains unclear. Thus, the aim of the present study was to investigate whether different concentrations of metabolic hormones are associated with different weight and BMI in infants beyond the first year of life. Methods: Milk samples at 2.6 (±0.4) months after birth and anthropometric measures at 13 months, 2, 3, and 5 years were collected as part of the Finnish STEPS cohort study from 501 mothers and the respective 507 infants. Leptin, adiponectin, insulin-like growth factor (IGF)-1 and cyclic glycine-proline (cGP) in milk were analyzed. Multiple regression models and a repeated measures mixed model were used to examine associations between milk hormone concentrations and weight and BMI z-scores across time, at each time-point, and weight gain from birth to each follow-up visit. All models were corrected for birth weight, infant sex, duration of exclusive and total breastfeeding, time of introduction of solid foods and maternal pre-pregnancy BMI. Results: Higher milk IGF-1 was associated with higher weight at 13 months (p = 0.004) but lower weight at 3 (p = 0.011) and 5 years of age (p = 0.049). Higher cGP was associated with lower weight across the 5 years (p = 0.019) but with higher BMI at 5 years (p = 0.021). Leptin and adiponectin did not display associations with infant growth at this time. Sex interactions were also absent. Conclusions: Our results suggest that the interplay between human milk-borne IGF-1 and cGP is similar to that reported in other mammals and may have an important role Galante et al. Breastmilk IGF-1 and Infant Growth in defining infant growth trajectories beyond the first year of life. Further research should explore the determinants and origins of these milk-borne compounds and evaluate their effect on infant growth and metabolism.

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Section: Discussionsupporting

confidence: 66%

Growth Factor Concentrations in Human Milk Are Associated With Infant Weight and BMI From Birth to 5 Years

et al. 2020

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“…Given that maternal HMOs content and composition are known to differ by donors, [6] it is plausible that the effects seen may not extend to all milk donors of the current study. This is especially important in the clinical context where HMOs diversity, as opposed to the availability of single agents, [18,40,41] appears to mediate the protective effects against the development of NEC on individual basis. Therefore, future studies should explore the relationship between donor-specific diversity composition and host intestinal signaling.…”

Section: Discussionmentioning

confidence: 99%

Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Activating Intestinal Cell Differentiation

Horne

et al. 2020

Molecular Nutrition Food Res

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Scope: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency and currently the leading cause of mortality in preterm infants. Recent studies show that human milk oligosaccharides (HMOs) reduce the frequency and incidence of NEC; however, the molecular mechanisms for their protection are largely unexplored. Methods and results: To address this gap, a genome-wide profiling of the intestinal epithelial transcriptome in response to HMOs using RNA-sequencing is performed. It is found that HMOs alter the host transcriptome in 225 unique target genes pertaining to cell proliferation and differentiation, including upregulation of stem cell differentiation marker HMGCS2. To validate these results, differentiation in Caco-2Bbe1 (Caco-2) intestinal cells is verified by Alcian Blue staining and transepithelial electrical resistance (TER) recordings. Furthermore, an in vivo model of NEC is also employed whereby neonatal pups are gavage fed HMOs. Interestingly, HMOs-fed pups show enhanced cell MUC2 differentiation and HMGCS2 expression. Conclusions: These findings demonstrate HMOs protect against NEC in part by altering the differentiation of the crypt-villus axis. In addition, this study suggests that pooled HMOs directly induce a series of biological processes, which provide mechanistic insights to how HMOs protect the host intestine.

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“…2 ′ -FL seems directly associated to maternal pre-pregnancy BMI, infant weight up to 1 year of life and also child height up to 5 years of life in offspring of Se+ mothers. According to such data, this HMOs seems to affect child growth up to 5 years of life (92).…”

Section: Monosaccharides and Oligosaccharidesmentioning

confidence: 92%

The Human Breast Milk Metabolome in Overweight and Obese Mothers

et al. 2020

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Pre-pregnancy body mass index (BMI) is a major relevance factor, since maternal overweight and obesity can impair the pregnancy outcome and represent risk factors for several neonatal, childhood, and adult conditions, including excessive weight gain, cardiovascular disease, diabetes mellitus, and even behavioral disorders. Currently, breast milk (BM) composition in such category of mothers was not completely defined. In this field, metabolomics represents the ideal technology, able to detect the whole profile of low molecular weight molecules in BM. Limited information is available on human BM metabolites differences in overweight or obese compared to lean mothers. Analyzing all the metabolomics studies published on Medline in English language, this review evaluated the effects that 8 specific types of metabolites found altered by maternal overweight and obesity (nucleotide derivatives, 5-methylthioadenosine, sugar-alcohols, acylcarnitine and amino acids, polyamines, mono-and oligosaccharides, lipids) can exert on the risk of offspring obesity development and other potentially associated health outcomes and complications. However, metabolites variations in samples collected from overweight and obese mothers and the potentially correlated effects highlighted below still need further investigations and should be confirmed in future metabolomics studies on larger samples. Finally, the positive or negative influence of maternal overweight and obesity on the offspring, potentially exerted by breastfeeding, should be analyzed in close correlation with maternal age, genetic and environmental factors, including diet, and taking into account the interactions occurring between BM metabolites and lactobiome. The evaluation of all the factors affecting BM metabolites in overweight and obese mothers can lead to the comprehensive description of such biofluid and the related effects on breastfed subjects, potentially highlighting personalized needs of BM supplementation or short-and long-term prevention strategies to optimize offspring health.

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Associations between human milk oligosaccharides and growth in infancy and early childhood

Cited by 89 publications

References 32 publications

Growth Factor Concentrations in Human Milk Are Associated With Infant Weight and BMI From Birth to 5 Years

Growth Factor Concentrations in Human Milk Are Associated With Infant Weight and BMI From Birth to 5 Years

Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Activating Intestinal Cell Differentiation

The Human Breast Milk Metabolome in Overweight and Obese Mothers

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