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Proceedings of the National Academy of... Jul 2023Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar...
Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar -inositol as a component that promotes brain development. We determined that it is most abundant in human milk during early lactation when neuronal connections rapidly form in the infant brain. -inositol promoted synapse abundance in human excitatory neurons as well as cultured rat neurons and acted in a dose-dependent manner. Mechanistically, -inositol enhanced the ability of neurons to respond to transsynaptic interactions that induce synapses. Effects of -inositol in the developing brain were tested in mice, and its dietary supplementation enlarged excitatory postsynaptic sites in the maturing cortex. Utilizing an organotypic slice culture system, we additionally determined that -inositol is bioactive in mature brain tissue, and treatment of organotypic slices with this carbocyclic sugar increased the number and size of postsynaptic specializations and excitatory synapse density. This study advances our understanding of the impact of human milk on the infant brain and identifies -inositol as a breast milk component that promotes the formation of neuronal connections.
Topics: Female; Infant; Humans; Animals; Mice; Rats; Milk, Human; Breast Feeding; Neurons; Inositol; Sugars
PubMed: 37433002
DOI: 10.1073/pnas.2221413120 -
Nutrients Aug 2023Human milk oligosaccharides (HMOs) are a major component of human milk. They are associated with multiple health benefits and are manufactured on a large scale for their... (Review)
Review
Human milk oligosaccharides (HMOs) are a major component of human milk. They are associated with multiple health benefits and are manufactured on a large scale for their addition to different food products. In this systematic review, we evaluate the health outcomes of published clinical trials involving the supplementation of manufactured HMOs. We screened the PubMed database and Cochrane Library, identifying 26 relevant clinical trials and five publications describing follow-up studies. The clinical trials varied in study populations, including healthy term infants, infants with medical indications, children, and adults. They tested eight different HMO structures individually or as blends in varying doses. All trials included safety and tolerance assessments, and some also assessed growth, stool characteristics, infections, gut microbiome composition, microbial metabolites, and biomarkers. The studies consistently found that HMO supplementation was safe and well tolerated. Infant studies reported a shift in outcomes towards those observed in breastfed infants, including stool characteristics, gut microbiome composition, and intestinal immune markers. Beneficial gut health and immune system effects have also been observed in other populations following HMO supplementation. Further clinical trials are needed to substantiate the effects of HMO supplementation on human health and to understand their structure and dose dependency.
Topics: Adult; Child; Infant; Female; Humans; Milk, Human; Breast Feeding; Commerce; Oligosaccharides; Dietary Supplements
PubMed: 37630811
DOI: 10.3390/nu15163622 -
Cell Host & Microbe Sep 2023Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced...
Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol sulfate, metabolites that impact host inflammatory status. Furthermore, Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts lactate produced by B. infantis to propionate, an important mediator of host physiology. These results suggest that the synbiotic reproducibly and predictably modulates recovery of a dysbiotic microbiome.
Topics: Infant; Humans; Adult; Gastrointestinal Microbiome; Dysbiosis; Milk, Human; Synbiotics; Microbiota; Lactic Acid; Veillonella
PubMed: 37657443
DOI: 10.1016/j.chom.2023.08.004 -
MCN. the American Journal of Maternal...
Topics: Female; Humans; Breast Feeding; Milk, Human
PubMed: 37840206
DOI: 10.1097/NMC.0000000000000958 -
Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A.The Journal of Experimental Medicine Aug 2023Immunoglobulin A (IgA) is secreted into breast milk and is critical for both protecting against enteric pathogens and shaping the infant intestinal microbiota. The...
Immunoglobulin A (IgA) is secreted into breast milk and is critical for both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity; however, heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity between all donors, independent of preterm or term delivery. Surprisingly, we also observed intradonor variability in the BrmIgA response to closely related bacterial isolates. Conversely, longitudinal analysis showed that the antibacterial BrmIgA reactivity was relatively stable through time, even between sequential infants, indicating that mammary gland IgA responses are durable. Together, our study demonstrates that the antibacterial BrmIgA reactivity displays interindividual heterogeneity but intraindividual stability. These findings have important implications for how breast milk shapes the development of the preterm infant microbiota and protects against necrotizing enterocolitis.
Topics: Infant; Female; Infant, Newborn; Humans; Milk, Human; Infant, Premature; Immunoglobulin A; Bacteria; Anti-Bacterial Agents
PubMed: 37462916
DOI: 10.1084/jem.20220839 -
Breastfeeding Medicine : the Official... Dec 2023Mother's own milk is recognized as the optimal feeding not only for term but also for preterm infants. In addition to risk reduction for sepsis, necrotizing... (Review)
Review
Mother's own milk is recognized as the optimal feeding not only for term but also for preterm infants. In addition to risk reduction for sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity in the early infancy, feeding preterm infants with mother's own milk is also associated with a better neurodevelopmental outcome; lower rates of otitis media, gastroenteritis, and respiratory infections; and a reduced risk of cardiovascular disease, obesity, and diabetes later in life. Donor human milk is the best alternative if mother's own milk is not available or with short supply. There is growing evidence that the benefits of human milk are mediated by the human milk microbiota and by human milk oligosaccharides through their influence on the infant's gut microbiota. Unfortunately, although human milk contains beneficial bacteria, it may also contain pathogenic bacteria. The antimicrobial properties of human milk protect those infants fed with their own mother's raw milk. In donor human milk, however, the antimicrobial activity is diminished due to storage and in particular by pasteurization, hereby lowering the resistance against bacterial infections. Subsequently, microbiological screening of donor human milk might enhance its safety for preterm infants. Up to date, a consensus on recommendations for the microbiological testing of donor human milk is lacking. Existing local and national guidelines for the microbiological screening vary significantly in terms of timing and frequency of testing as well as their specific acceptance and discard criteria. We reviewed the literature about microbiological testing of donor human milk to provide evidence-based recommendations for donor human milk.
Topics: Infant; Female; Infant, Newborn; Humans; Milk, Human; Infant, Premature; Infant Nutritional Physiological Phenomena; Breast Feeding; Anti-Infective Agents
PubMed: 37971784
DOI: 10.1089/bfm.2023.0155 -
Nutrients Nov 2023Premature infants, given their limited reserves, heightened energy requirements, and susceptibility to nutritional deficits, require specialized care. (Review)
Review
UNLABELLED
Premature infants, given their limited reserves, heightened energy requirements, and susceptibility to nutritional deficits, require specialized care.
AIM
To examine the complex interplay between nutrition and neurodevelopment in premature infants, underscoring the critical need for tailored nutritional approaches to support optimal brain growth and function.
DATA SOURCES
PubMed and MeSH and keywords: preterm, early nutrition, macronutrients, micronutrients, human milk, human milk oligosaccharides, probiotics AND neurodevelopment or neurodevelopment outcomes. Recent articles were selected according to the authors' judgment of their relevance. Specific nutrients, including macro (amino acids, glucose, and lipids) and micronutrients, play an important role in promoting neurodevelopment. Early and aggressive nutrition has shown promise, as has recognizing glucose as the primary energy source for the developing brain. Long-chain polyunsaturated fatty acids, such as DHA, contribute to brain maturation, while the benefits of human milk, human milk oligosaccharides, and probiotics on neurodevelopment via the gut-brain axis are explored. This intricate interplay between the gut microbiota and the central nervous system highlights human milk oligosaccharides' role in early brain maturation.
CONCLUSIONS
Individualized nutritional approaches and comprehensive nutrient strategies are paramount to enhancing neurodevelopment in premature infants, underscoring human milk's potential as the gold standard of nutrition for preterm infants.
Topics: Infant; Female; Infant, Newborn; Humans; Infant, Premature; Infant Nutritional Physiological Phenomena; Milk, Human; Fatty Acids; Micronutrients; Oligosaccharides; Glucose
PubMed: 37960297
DOI: 10.3390/nu15214644 -
Cadernos de Saude Publica 2023The objective of this study was to describe the frequency of cross-breastfeeding, human milk donation to human milk banks and reception of human milk from human milk...
The objective of this study was to describe the frequency of cross-breastfeeding, human milk donation to human milk banks and reception of human milk from human milk banks, and to investigate the intersection between cross-breastfeeding and breast milk donation practices. This study used data from the national household-based survey Brazilian National Survey on Child Nutrition (ENANI-2019), which collected information from 14,558 children < 5 years old between February 2019 and March 2020. The present study included data from 5,831 biological mothers who reported having breastfed their child < 2 years old at least once and replied questions about cross-breastfeeding, donation and recaption of human milk to human milk banks. Prevalence and 95% confidence intervals (95%CI) were estimated for each stratifier, considering the study complex sample design. Among mothers of children < 2 years old who breastfed their child at least once, 21.1% practiced cross-breastfeeding; breastfeeding another child was more frequent (15.6%) than allowing a child to be breastfed by another woman (11.2%). Among this population, 4.8% of women donated human milk to a human milk bank, and 3.6% reported that their children had received donated human milk. The donation of human milk is a practice recommended by the Brazilian Ministry of Health and has the potential to save thousands of newborns throughout Brazil. In contrast, cross-breastfeeding is contraindicated due to the potential risk of transmitting HIV. There is a need for a broad debate on these practices in Brazil and worldwide.
Topics: Child; Infant, Newborn; Female; Humans; Infant; Child, Preschool; Breast Feeding; Brazil; Milk, Human; Milk Banks; Mothers
PubMed: 37792877
DOI: 10.1590/0102-311XEN082322 -
Hormones and Behavior Jul 2023The Developmental Origins of Health and Disease (DOHaD) hypothesis describes how maternal stress exposures experienced during critical periods of perinatal life are... (Review)
Review
The Developmental Origins of Health and Disease (DOHaD) hypothesis describes how maternal stress exposures experienced during critical periods of perinatal life are linked to altered developmental trajectories in offspring. Perinatal stress also induces changes in lactogenesis, milk volume, maternal care, and the nutritive and non-nutritive components of milk, affecting short and long-term developmental outcomes in offspring. For instance, selective early life stressors shape the contents of milk, including macro/micronutrients, immune components, microbiota, enzymes, hormones, milk-derived extracellular vesicles, and milk microRNAs. In this review, we highlight the contributions of parental lactation to offspring development by examining changes in the composition of breast milk in response to three well-characterized maternal stressors: nutritive stress, immune stress, and psychological stress. We discuss recent findings in human, animal, and in vitro models, their clinical relevance, study limitations, and potential therapeutic significance to improving human health and infant survival. We also discuss the benefits of enrichment methods and support tools that can be used to improve milk quality and volume as well as related developmental outcomes in offspring. Lastly, we use evidence-based primary literature to convey that even though select maternal stressors may modulate lactation biology (by influencing milk composition) depending on the severity and length of exposure, exclusive and/or prolonged milk feeding may attenuate the negative in utero effects of early life stressors and promote healthy developmental trajectories. Overall, scientific evidence supports lactation to be protective against nutritive and immune stressors, but the benefits of lactation in response to psychological stressors need further investigation.
Topics: Infant; Female; Pregnancy; Animals; Humans; Breast Feeding; Lactation; Milk, Human; Mothers; Parents
PubMed: 37269591
DOI: 10.1016/j.yhbeh.2023.105375 -
The Journal of Dairy Research Nov 2023This study aimed to determine lactoferrin (LF) in breast milk-based powders and formulas. Lactoferrin is an important whey protein in all mammalian milks and is...
This study aimed to determine lactoferrin (LF) in breast milk-based powders and formulas. Lactoferrin is an important whey protein in all mammalian milks and is responsible in large part for the known antimicrobial effects of human milk in particular. As breast feeding is not always possible, formulas based on cows milk have been developed in order to meet the nutritional needs of the newborn, while more recently human breast milk-based powders have been introduced to offer the biological functionality of human milk to pre-term and critically ill babies. In the present work, the amount of LF in commercial breast milk-based powders was tested by a validated RF-HPLC method for the determination of LF in breast milk in order to examine both the applicability of the method but at a second level the amount of LF in these commercial products. The detection of LF was possible but the complexity of the matrix lead us to the use the standard addition methodology in order to achieve quantification. The results indicated that breast milk-based powders had higher amount of LF than cows milk-based formulas, both non-fortified and fortified.
Topics: Infant; Female; Humans; Cattle; Animals; Milk, Human; Milk; Lactoferrin; Powders; Breast Feeding; Chromatography, High Pressure Liquid; Mammals
PubMed: 38214140
DOI: 10.1017/S0022029923000778