Ultrasound modification on milk fat globule membrane and soy lecithin to improve the physicochemical properties, microstructure and stability of mimicking human milk fat emulsions.

Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.

Revealing the diversity of endogenous peptides and parent proteins in human colostrum and mature milk through peptidomics analysis.

Endogenous peptides and their parent proteins are important nutritional components with diverse biological functions. The objective of this study was to analyze and compare endogenous peptides and parent proteins found in human colostrum (HC) and human mature milk (HM) using a 4D label-free technique. In total, 5162 and 940 endogenous peptides derived from 258 parent proteins were identified in human milk by database (DB) search and de novo, respectively. Among these peptides, 2446 differentially expressed endogenous peptides with various bioactivities were identified. The Gene Ontology analysis unveiled the cellular components, biological processes, and molecular functions associated with these parent proteins. Metabolic pathway analysis suggested that neutrophil extracellular trap formation had the greatest significance with 24 parent proteins. These findings will offer a fresh perspective on the development of infant formula powder, highlighting the potential for incorporating these changes to enhance its nutritional composition and benefits.

The triacylglycerol structures are key factors influencing lipid digestion in preterm formulas during in vitro digestion.

Preterm formulas are usually supplemented with medium-chain triacylglycerols (MCT) whereas breast milk contains more medium and long-chain triacylglycerols (MLCT). Different types of triacylglycerol (TAG) containing medium-chain fatty acids may influence lipid digestion. In this study, the digestive characteristics of breast milk and preterm formulas with different MCT contents were evaluated using a dynamic in vitro system simulating the gastrointestinal tract of preterm infants. The lipolysis products, including diacylglycerols, monoacylglycerols (MAGs), free fatty acids, and undigested TAGs, were analyzed. Formulas with MCT addition has significantly (P < 0.05) lower lipolysis degree (LD, 69.35%-71.28%) than breast milk (76.93%). Higher amounts of C8:0 and C10:0 were released in the formulas with MCT addition. Breast milk released more C18:1n-9, C18:2n-6, and MAG containing C16:0, whereas formulas released more free C16:0. The Pearson correlation heatmap showed that the LD value was significantly and positively (P < 0.05) related to the MLCT and sn-2 C16:0 content.

Relationship Between Maternal Age and Macronutrient Content of Colostrum.

BACKGROUND: Little is known about the relationship between maternal age and the macronutrient content of colostrum. RESEARCH AIMS: This study aimed to evaluate the relationship between maternal age and human milk macronutrient content by comparing the concentrations of lactose, proteins, and lipids in the colostrum of women with younger, moderate, and advanced maternal age. METHODS: An observational, cross-sectional study was designed to compare the macronutrient concentrations in the colostrum of women aged < 20 years, 20 to 34 years, and > 34 years (younger, moderate, and advanced maternal age, respectively; n = 33 per group). For each participant, 3 ml of colostrum was collected by manual extraction from the right breast at 10 am, 39-48 hr after delivery, and analyzed using a Miris Human Milk Analyzer. Macronutrient concentrations were compared between the groups using analysis of variance. P < 0.05 was considered significant. RESULTS: Mothers with moderate maternal age had a higher colostrum lipid concentration than those with younger or advanced maternal age (2.3 mg, SD = 1.4 mg vs. 1.5 mg, SD = 1.0 mg vs. 1.6 mg, SD = 0.9 mg, respectively; p = 0.007). Lactose and protein contents in the analyzed samples did not differ among the three study groups. CONCLUSION: This study lends support to the potential variation of lipids in colostrum by maternal age and suggests individual adaptation to the nutritional components of milk to the needs of the infant may be beneficial.

Probabilistic risk assessment for determining nonessential metals in commercial infant formula products in Taiwan.

During the early months of life, infant formula plays a crucial role as a primary source of both food and essential nutrients for infants, serving as a replacement for or supplement to breast milk. However, nonessential metals in infant formulas are a concern because infants are highly vulnerable to chemical exposure. The aim of this study was to investigate infant exposure to nonessential metals in infant formula products in Taiwan and assess the associated health risks. In this study, concentrations of arsenic (As), barium (Ba), cadmium (Cd), manganese (Mn), lead (Pb), and vanadium (V) in 45 formula products for 0-1-year-old infants were determined by inductively coupled plasma mass spectrometry. The mean As, Ba, Cd, Mn, Pb, and V concentrations were 6.42, 280, 3.72, 1425, 20.4, and 21.9 µg/kg, respectively. According to our probabilistic simulation of the estimated daily intake of metals, the proportion of hazard quotients exceeding one was 7.69% for As and 3.29% for Mn, and that of hazard index (HI) values exceeding 1 was >17% for metals. Arsenic had the largest HI contribution (46.9%), followed by Mn (22.3%) and Pb (12.7%). The nonessential metals content in infant formula raises potential noncarcinogenic health concerns for infants in Taiwan. Therefore, regulations for nonessential metals must be imposed on related food products in Taiwan, with a particular focus on As and Mn.

Sialic acid in human milk and infant formulas in China: concentration, distribution and type.

This study compared the concentrations, types and distributions of sialic acid (SA) in human milk at different stages of the postnatal period with those in a range of infant formulas. Breast milk from mothers of healthy, full-term and exclusively breastfed infants was collected on the 2nd (n 246), 7th (n 135), 30th (n 85) and 90th (n 48) day after birth. The SA profiles of human milk, including their distribution, were analysed and compared with twenty-four different infant formulas. Outcome of this observational study was the result of natural exposure. Only SA of type Neu5Ac was detected in human milk. Total SA concentrations were highest in colostrum and reduced significantly over the next 3 months. Approximately 68·7­76·1 % of all SA in human milk were bound to oligosaccharides. Two types of SA, Neu5Ac and Neu5Gc, have been detected in infant formulas. Most SA was present in infant formulas combined with protein. Breastfed infants could receive more SA than formula-fed infants with the same energy intake. Overall, human milk is a preferable source of SA than infant formulas in terms of total SA content, dynamics, distribution and type. These SA profiles in the natural state are worth to be considered by the production of formulas because they may have a great effect on infant nutrition and development.

Online LC-ESI-MS/MS comparative analysis of N/O-glycopatterns in human colostrum from different ethnic groups in Northwest China.

Human milk oligosaccharides, including free oligosaccharides and glycoconjugates, exert a key role in neonatal health and development. Changes in free oligosaccharides of milk from different ethnic groups have been documented. In this study, human milk was collected from Han, Hui, and Tibetan populations in northwest China, and differences in N/O-glycome among these three ethnic groups were systematically compared using online high-performance liquid chromatography-tandem mass spectrometry. Among the 63 detected N-glycans, 35 showed significant differences between the three ethnic groups (p < 0.05). Among the 70 detected O-glycans, four neutral O-glycans and six acidic O-glycans exhibited significant differences among the three ethnic groups (p < 0.05), with six acidic O-glycans reported for the first time. Overall, the extent of milk N/O-glycosylation was higher in the Han population than in the Hui or Tibetan groups. This trend was particularly pronounced for the main sialylated N/O-glycans. Except for sulfated O-glycans, which were higher in the milk from Tibetan mothers, the other types of N/O-glycans were present in similar proportions across all ethnic groups. Understanding the composition of N/O-glycans in human milk can help research on the structure-function relationship of glycans.

More than nutrition: Therapeutic potential and mechanism of human milk oligosaccharides against necrotizing enterocolitis.

Human milk is the most valuable source of nutrition for infants. The structure and function of human milk oligosaccharides (HMOs), which are key components of human milk, have long been attracting particular research interest. Several recent studies have found HMOs to be efficacious in the prevention and treatment of necrotizing enterocolitis (NEC). Additionally, they could be developed in the future as non-invasive predictive markers for NEC. Based on previous findings and the well-defined functions of HMOs, we summarize potential protective mechanisms of HMOs against neonatal NEC, which include: modulating signal receptor function, promoting intestinal epithelial cell proliferation, reducing apoptosis, restoring intestinal blood perfusion, regulating microbial prosperity, and alleviating intestinal inflammation. HMOs supplementation has been demonstrated to be protective against NEC in both animal studies and clinical observations. This calls for mass production and use of HMOs in infant formula, necessitating more research into the safety of industrially produced HMOs and the appropriate dosage in infant formula.

The Gestational Pathologies Effect on the Human Milk Redox Homeostasis: A First Step towards Its Definition.

BACKGROUND: Human Milk (HM) is a dynamic nourishment; its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important to evaluate the impact that gestational pathologies have on HM components and if their presence, as a source of oxidative stress in the mother, influence milk's redox homeostasis. To assess the effect of Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) on some aspects of human milk redox homeostasis, we chose to investigate both oxidative and antioxidant aspects, with, respectively, Lipid hydroperoxides (LOOHs) and Glutathione (GSH). METHODS: Women with PE, GDM and who were healthy were recruited for this study. Colostrum, transitional and mature milk samples were collected. GSH and LOOHs levels were measured using a spectrophotometric test. To investigate the effect of pathology on redox homeostasis, a mixed linear model with unistructural covariance structure was performed. RESULTS: A total of 120 mothers were recruited. The GSH concentration results were significantly lower in GDM women than in healthy women only in colostrum (p < 0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. DISCUSSION: Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the GSH level of HM, mainly in colostrum.

The Influence of Early Nutrition on Neurodevelopmental Outcomes in Preterm Infants.

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.

Trace elements status in human breast milk of mothers from Île-de-France region.

Breastfeeding is the main source of nutrition during first months of life. Its composition varies according to parameters like mother's diet and health, living area, number of pregnancies and lactation duration… Trace-elements concentration in breastmilk is then an important parameter that can affect infant's health, growth or immune system and organ functions. Few data are available on this topic, and results are often very variable. The aim of this work is to determine reference values of Copper (Cu), Zinc (Zn), Selenium (Se), Cobalt (Co), Iron (Fe) and Iodine (I) in human breastmilk according to lactation duration and to study influencing parameters on its elementary composition. Regional Human Milk Bank of Necker Enfants Malades Hospital provided samples that came from breastfeeding woman involved in voluntary milk donation and epidemiologic data. Two hundred thirty-two breastmilk were analysed. After nitric acid mineralization of milk samples, Cu, Zn, Se, Co and I were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in a standard mode. Fe was measured by Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Both assays were validated in terms of sensitivity, repeatability and accuracy.Studied breast milks came from mothers with an average age of 32 years and donation time ranged from one day after childbirth to 974 days (> 2.5 years); mean lactation duration is 59 days (> 8 weeks) while median duration is 29 days (around 4 weeks). In all studied samples, mean results and reference values are for Cu: 6.02 (1.71-13.23), Zn: 43.86 (7.3-107.0), Se: 0.12 (0.07-0.24), I: 0.29 (0.07-1.01) and Fe: 4.72 (1.25-11.49) µmol/L and for Co: 12.28 (5.27-25.82) nmol/L. Important number of studied milks allowed their distribution into seven classes of lactation durations. Samples were divided into four successive classes of fifteen days after childbirth, two other classes corresponding to the 3rd and 4th months and a last class for milks sampled after 4 months of lactation. Results were analysed in each class allowing study of evolution during lactation. That was particularly interesting for Zn, that presented an important variability in the total population (4-132 µmol/L) explained by variation along lactation evolution decreasing from 48 to 17 µmol/L in first and last duration classes respectively. In addition, Cu and Fe concentrations were also significantly correlated with lactation duration while Se and I were in a lesser extent (p = 0.002). In this study, we present reference values for studied trace elements at different lactation stages, allowing a fine interpretation of future breast milk samples results according to their sampling time. By continuing this study, we plan to increase number of samples in some of the classes and to study the influence of premature birth or twin pregnancy on breast milk elementary composition.

Human Milk Nutrient Composition Data is Critically Lacking in the United States and Canada: Results from a Systematic Scoping Review of 2017-2022.

Characterization of the nutrients in human milk is important to understand the dietary and developmental requirements of infants. The objective of this review was to summarize the state-of-the-science on the nutrient composition of human milk in the United States and Canada published from 2017 to 2022. Four databases were searched for randomized controlled studies and others given the scoping nature of this review. We limited type to mature milk collected 21 d postpartum and beyond from lactating individuals in the United States and Canada who gave birth at 37-wk gestation or later (full-term). Outcomes of interest included traditional macro- and micronutrients, including human milk oligosaccharides (HMOs), and milk volume. The publication date range was selected as January 1, 2017, to the day the literature search was performed. A total of 32 articles were included in the scoping review from primarily longitudinal cohort or cross-sectional designs. The most prevalent sample collection method was full-breast expression (n = 20) with most studies (n = 26) collecting samples from a single timepoint. Carbohydrates (HMOs [n = 12], glucose [n = 8], and lactose [n = 6]) and protein (n = 5) were the most frequently assessed nutrients in this body of work, with consensus among studies that glucose is present in limited concentrations compared to lactose (24-64 mg/dL compared with 6-7 g/dL) and that HMOs are influenced by temporality and secretor status. Included studies displayed an overall level of heterogeneity and sparsity paralleling previous reports and nutrient data in the USDA FoodData Central system. Much of the data extracted from retained articles generally provided analysis of a specific nutrient or group of nutrients. Moreover, many studies did not use the preferred analytical methods as outlined by the Human Milk Composition Initiative to increase measurement confidence. Up-to-date nutrient composition data of human milk is still greatly needed as it is paramount for the management of infant feeding, assessment of infant and maternal nutritional and health needs, and as a reference for infant formula development.

Proteomic analysis of exosomes derived from human mature milk and colostrum of mothers with term, late preterm, or very preterm delivery.

The growth and development of the human brain is a long and complex process that requires a precise sequence of genetic and molecular events. This begins in the third week of gestation with the differentiation of neural progenitor cells and extends at least until late adolescence, possibly for life. One of the defects of this development is that we know very little about the signals that modulate this sequence of events. The first 3 years of life, during breastfeeding, is one of the critical periods in brain development. In these first years of life, it is believed that neurodevelopmental problems may be the molecular causes of mental disorders. Therefore, we herein propose a new hypothesis, according to which the chemical signals that could modulate this entire complex sequence of events appear in this early period, and the molecular level study of human breast milk and colostrum of mothers who give birth to children in different gestation periods could give us information on proteins influencing this process. In this work, we collected milk and colostrum samples (term, late preterm and moderate/very preterm) and exosomes were isolated. The samples of exosomes and complete milk from each fraction were analyzed by LC-ESI-MS/MS. In this work, we describe proteins in the different fractions of mature milk and colostrum of mothers with term, late preterm, or very preterm delivery, which could be involved in the regulation of the nervous system by their functions. We describe how they differ in different types of milk, paving the way for the investigation of possible new neuroregulatory pathways as possible candidates to modulate the nervous system.

Breastmilk cadmium levels and estimated infant exposure: a multicenter study of associated factors in a resource-limited country.

BACKGROUND: Despite the undisputed benefits of breastfeeding, infants might become exposed to xenobiotics that could be excreted into breast milk following maternal exposure. This study was conducted to assess breastmilk cadmium levels among lactating women in Palestine, a resource-limited country. Estimated daily intake (EDI) of cadmium via breastmilk was also calculated and predictors of high breastmilk cadmium levels and high infant exposure via breastmilk were identified. METHODS: This multicenter study was conducted using a descriptive-analytical design. The lactating women were recruited from different maternity and public health clinics in all regions of Palestine. Demographic variables and exposure to sources of cadmium were collected in an interviewer-administered questionnaire. Foremilk samples (about 5 mL) were collected in polyethylene tubes using the hand-expression technique. The breast milk samples were collected in the period between December 2020 and March 2021. A pre-validated method using inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify breastmilk cadmium levels. EDI values were calculated from the quantified breastmilk cadmium levels. RESULTS: Breastmilk samples were obtained from 256 lactating women. The mean breastmilk cadmium level was 0.34 (SD: 0.33) µg / L and the mean EDI of cadmium via breastmilk was 0.059 (SD: 0.058) µg / kg per body weight / day. Breastmilk cadmium levels were quantified in 92.6% of the breastmilk samples. Of the breastmilk samples, 13 (5.1%) had cadmium levels above those reported as "normal" by the World Health Organization (WHO). Multiple linear regression showed that higher breastmilk cadmium levels and higher EDI were predicted by being a smoker, living in a refugee camp, living close to an industrial area, living close to disposal of wastes, living close to paint shops, living in a house with peeling / chipping paint, frequent use of cosmetics, frequent use of hair dyes, and not using vitamins. CONCLUSION: The breastmilk cadmium levels and infant exposure were predicted by maternal exposure to sources of cadmium. The findings reported in this study are valuable to antenatal and postnatal healthcare service providers. More studies are needed to plan and implement measures to reduce breastmilk cadmium levels and infants' exposure to cadmium via breastmilk.

Human preterm colostrum stimulates outgrowth in neurogenic tissue.

BACKGROUND: The olfactory bulb has a key role for nasal delivery of drugs to the brain by its access from the nasal mucosa and its connection to the subventricular zone. The aim of this study was to investigate the neuromodulatory capacity of human milk of premature infants on the olfactory bulb. METHODS: Olfactory bulbs from P1 mice were embedded in a collagen I gel and incubated with DMEM supplemented with the aqueous phase of human colostrum (Col) of five mothers after very preterm birth, mature milk (Mat) of the same mothers or without supplement (Ctrl). After 7 days, the neurite outgrowth was quantified. Proteome analysis of the milk samples was performed using unlabeled mass spectrometry. RESULTS: Outgrowth increased significantly in bulbs exposed to Col but not when exposed to Mat. Mass spectrometry revealed profound differences in the proteome of Col versus Mat. Among 21 upregulated proteins in Col were proteins involved in neurite outgrowth, axon guidance, neuromodulation and longevity. CONCLUSIONS: A high bioactivity of human preterm colostrum on murine neonatal neurogenic tissue is demonstrated to be associated with a proteome profoundly differing from mature milk. IMPACT: The hypothesis has been raised that neonatal brain damage in a preterm infant could potentially be ameliorated by intranasal application of maternal breast milk. In an in-vitro model using neonatal murine olfactory bulb explants a significant stimulatory effect by human preterm colostrum is observed. Proteomics reveals upregulated neuroactive proteins in human colostrum compared to mature milk. A confirmation of this exploratory study would indicate that preterm colostrum stimulates neurogenic tissue. Early intranasal colostrum application might attenuate perinatal loss of neurogenic tissue thereby contributing to reducing complications such as cerebral palsy.

Lipid Peroxidation and Antioxidative Capacity Are Unaltered in Transitional Breast Milk Exposed to Light from Women Giving Birth to Preterm Infants before 32 Weeks of Gestation.

Breast milk (BM) is the primary nutrition for infants and has a high content of lipids. Preterm infants receive expressed BM via tube feeding, and they are frequently treated with phototherapy. When parenteral nutrition (PN) is exposed to light and/or phototherapy, lipid peroxidation (LPO) increases. By light-protecting PN, morbidity and mortality are reduced in preterm infants through the reduction of oxidative stress. We aimed to investigate whether light-protecting breast milk could reduce LPO. Twelve mothers giving birth to a preterm infants of less than 32 weeks of gestational age were included. Transitional BM was collected and divided into three study groups; light-protected, ward light and phototherapy light. Baseline samples were collected after expression and the exposures started within one hour. Feeding syringe samples were exposed to light for 30 up to 360 min. Nasogastric tube samples were run through a tube under the same light conditions. Samples were stored in -80 °C until analyses of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and total antioxidant capacity (TAC). There were no significant differences in MDA, 4-HNE or TAC levels observed between the different study groups. This study indicates that the light exposure of expressed transitional BM does not affect LPO and the levels of MDA, 4-HNE or TAC.

Infants Fed Breastmilk or 2'-FL Supplemented Formula Have Similar Systemic Levels of Microbiota-Derived Secondary Bile Acids.

Human milk represents an optimal source of nutrition during infancy. Milk also serves as a vehicle for the transfer of growth factors, commensal microbes, and prebiotic compounds to the immature gastrointestinal tract. These immunomodulatory and prebiotic functions of milk are increasingly appreciated as critical factors in the development of the infant gut and its associated microbial community. Advances in infant formula composition have sought to recapitulate some of the prebiotic and immunomodulatory functions of milk through human milk oligosaccharide (HMO) fortification, with the aim of promoting healthy development both within the gastrointestinal tract and systemically. Our objective was to investigate the effects of feeding formulas supplemented with the HMO 2'-fucosyllactose (2'-FL) on serum metabolite levels relative to breastfed infants. A prospective, randomized, double-blinded, controlled study of infant formulas (64.3 kcal/dL) fortified with varying levels of 2'-FL and galactooligosaccharides (GOS) was conducted [0.2 g/L 2'-FL + 2.2 g/L GOS; 1.0 g/L 2'-FL + 1.4 g/L GOS]. Healthy singleton infants age 0-5 days and with birth weight > 2490 g were enrolled (n = 201). Mothers chose to either exclusively formula-feed or breastfeed their infant from birth to 4 months of age. Blood samples were drawn from a subset of infants at 6 weeks of age (n = 35-40 per group). Plasma was evaluated by global metabolic profiling and compared to a breastfed reference group (HM) and a control formula (2.4 g/L GOS). Fortification of control infant formula with the HMO 2'-FL resulted in significant increases in serum metabolites derived from microbial activity in the gastrointestinal tract. Most notably, secondary bile acid production was broadly increased in a dose-dependent manner among infants receiving 2'-FL supplemented formula relative to the control formula. 2'-FL supplementation increased secondary bile acid production to levels associated with breastfeeding. Our data indicate that supplementation of infant formula with 2'-FL supports the production of secondary microbial metabolites at levels comparable to breastfed infants. Thus, dietary supplementation of HMO may have broad implications for the function of the gut microbiome in systemic metabolism. This trial was registered at with the U.S. National library of Medicine as NCT01808105.

γ-Linolenic acid in maternal milk drives cardiac metabolic maturation.

Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production1,2. This adaptation is triggered in part by post-partum environmental changes3, but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied γ-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors4 (RXRs), ligand-regulated transcription factors that are expressed in cardiomyocytes from embryonic stages. Multifaceted genome-wide analysis revealed that the lack of RXR in embryonic cardiomyocytes caused an aberrant chromatin landscape that prevented the induction of an RXR-dependent gene expression signature controlling mitochondrial fatty acid homeostasis. The ensuing defective metabolic transition featured blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, leading to perinatal cardiac dysfunction and death. Finally, GLA supplementation induced RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in cardiomyocytes, both in vitro and in vivo. Thus, our study identifies the GLA-RXR axis as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism.

HMOs Exert Marked Bifidogenic Effects on Children's Gut Microbiota Ex Vivo, Due to Age-Related Bifidobacterium Species Composition.

Prebiotics are substrates that are selectively utilized by host microorganisms, thus conferring a health benefit. There is a growing awareness that interpersonal and age-dependent differences in gut microbiota composition impact prebiotic effects. Due to the interest in using human milk oligosaccharides (HMOs) beyond infancy, this study evaluated how HMOs [2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), 6'Sialyllactose (6'SL)] and blends thereof affect the microbiota of 6-year-old children (n = 6) and adults (n = 6), compared to prebiotics inulin (IN) and fructooligosaccharides (FOS). The ex vivo SIFR® technology was used, given its demonstrated predictivity in clinical findings. First, HMOs and HMO blends seemed to maintain a higher α-diversity compared to FOS/IN. Further, while 2'FL/LNnT were bifidogenic for both age groups, 3'SL/6'SL and FOS/IN were exclusively bifidogenic for children and adults, respectively. This originated from age-related differences in microbiota composition because while 3'SL/6'SL stimulated B. pseudocatenulatum (abundant in children), FOS/IN enhanced B. adolescentis (abundant in adults). Moreover, all treatments significantly increased acetate, propionate and butyrate (only in adults) with product- and age-dependent differences. Among the HMOs, 6'SL specifically stimulated propionate (linked to Bacteroides fragilis in children and Phocaeicola massiliensis in adults), while LNnT stimulated butyrate (linked to Anaerobutyricum hallii in adults). Indole-3-lactic acid and 3-phenyllactic acid (linked to immune health) and gamma-aminobutyric acid (linked to gut-brain axis) were most profoundly stimulated by 2'FL and HMO blends in both children and adults, correlating with specific Bifidobacteriaceae. Finally, 2'FL/LNnT increased melatonin in children, while 3'SL remarkably increased folic acid in adults. Overall, age-dependent differences in microbiota composition greatly impacted prebiotic outcomes, advocating for the development of age-specific nutritional supplements. HMOs were shown to be promising modulators in the adult, and particularly the children's microbiota. The observed HMO-specific effects, likely originating from their structural heterogeneity, suggest that blends of different HMOs could maximize treatment effects.

Profile of Human Milk Phospholipids at Different Lactation Stages with UPLC/Q-TOF-MS: Characterization, Distribution, and Differences.

Human milk phospholipids are important for the regular growth and development of infants. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) was employed to qualitatively and quantitatively analyze 277 phospholipid molecular species in 112 human milk samples to obtain a detailed profile of human milk phospholipids along the lactation stage. MS/MS fragmentation patterns of sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine were characterized in detail. Phosphatidylcholine is the most dominant group, followed by sphingomyelin. PC(18:0/18:2), SM(d18:1/24:1), PE(18:0/18:0), PS(18:0/20:4), and PI(18:0/18:2) showed the highest average concentration among all of the phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol molecular species, respectively. The fatty acids attached to the phospholipid molecules were mainly palmitic, stearic, oleic, and linoleic acids, and the plasmalogens decreased along the lactation stage. The increase of sphingomyelins and phosphatidylethanolamines and the decrease of phosphatidylcholines are the key changes from colostrum to transitional milk; the increase of lysophosphatidylcholines and lysophosphatidylethanolamines and the continuous decrease of phosphatidylcholines are the vital changes from transitional milk to mature milk.