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Early-life nutrition significantly impacts vaccination efficacy in infants, whose immune response to vaccines is weaker compared to adults. This study investigated vaccination efficacy in female C57Bl/6JOlaHsd mice (6 weeks old) fed diets with 0.7% galacto-oligosaccharides (GOS)/long-chain fructo-oligosaccharides (lcFOS) (9:1), 0.3% human milk oligosaccharides (HMOS), or a combination (GFH) for 14 days prior to and during vaccination. Delayed-type hypersensitivity (DTH) was measured by assessing ear swelling following an intradermal challenge. Influvac-specific IgG1 and IgG2a levels were assessed using ELISAs, while splenic T and B lymphocytes were analyzed for frequency and activation via flow cytometry. Additionally, cytokine production was evaluated using murine splenocytes co-cultured with influenza-loaded dendritic cells. Mice on the GFH diet showed a significantly enhanced DTH response ( p < 0.05), increased serological IgG1 levels, and a significant rise in memory B lymphocytes (CD27+ B220+ CD19+). GFH-fed mice also exhibited more activated splenic Th1 cells (CD69+ CXCR3+ CD4+) and higher IFN-γ production after ex vivo restimulation ( p < 0.05). These findings suggest that GOS/lcFOS and HMOS, particularly in combination, enhance vaccine responses by improving memory B cells, IgG production, and Th1 cell activation, supporting the potential use of these prebiotics in infant formula for better early-life immune development.

Milk is a biological fluid with a dynamic composition of micronutrients and bioactive molecules that serves as a vital nutrient source for infants. Milk composition is affected by multiple factors, including genetics, geographical location, environmental conditions, lactation phase, and maternal nutrition, and plays a key role in dictating its microbiome. This study addresses a less-explored aspect, comparing the microbial communities in human breast milk with those in mature milk from species that are used for milk consumption. Since mature animal milk is used as a supplement for both the infant (formula) and the child/adolescent, our main aim was to identify shared microbial communities in colostrum and mature human milk. Using 16S rRNA metagenomic sequencing, we focused on characterizing the milk microbiota in the Northern Greek population by identifying shared microbial communities across samples and comparing the relative abundance of prevalent genera. We analyzed ten human milk samples (from five mothers), with five collected three days postpartum (colostrum) and five collected thirty to forty days postpartum (mature milk) from corresponding mothers. To perform an interspecies comparison of human milk microbiota, we analyzed five goat and five bovine milk samples from a local dairy industry, collected fifty to seventy days after birth. Alpha diversity analysis indicated moderate diversity and stability in bovine milk, high richness in goat milk, and constrained diversity in breast milk. Beta diversity analysis revealed significant distinctions among mammalian species, emphasizing both presence/absence and abundance-based clustering. Despite noticeable differences, shared microbial components underscore fundamental aspects across all mammalian species, highlighting the presence of a core microbiota predominantly comprising the Proteobacteria, Firmicutes, and Actinobacteriota phyla. At the genus level, Acinetobacter , Gemella , and Sphingobium exhibit significant higher abundance in human milk compared to bovine and goat milk, while Pseudomonas and Atopostipes are more prevalent in animal milk. Our comparative analysis revealed differences and commonalities in the microbial communities of various mammalian milks and unraveled the existence of a common fundamental milk core microbiome. We thus revealed both species-specific and conserved microbial communities in human, bovine, and goat milk. The existence of a common core microbiome with conserved differences between colostrum and mature human milk underscores fundamental similarities in the microbiota of milk across mammalian species, which could offer valuable implications for optimizing the nutritional quality and safety of dairy products as well as supplements for infant health.

Background: Human milk oligosaccharides (HMOs), which are unique bioactive components in human milk, are increasingly recognized for their multifaceted roles in infant health. A deeper understanding of the nexus between HMOs and the gut-brain axis can revolutionize neonatal nutrition and neurodevelopmental strategies., Methods: We performed a narrative review using PubMed, Embase, and Google Scholar to source relevant articles. The focus was on studies detailing the influence of HMOs on the gut and brain systems, especially in neonates. Articles were subsequently synthesized based on their exploration into the effects and mechanisms of HMOs on these interconnected systems., Results: HMOs significantly influence the neonatal gut-brain axis. Specific concentrations of HMO, measured 1 and 6 months after birth, would seem to agree with this hypothesis. HMOs are shown to influence gut microbiota composition and enhance neurotransmitter production, which are crucial for brain development. For instance, 2'-fucosyllactose has been demonstrated to support cognitive development by fostering beneficial gut bacteria that produce essential short-chain fatty acids., Conclusions: HMOs serve as crucial modulators of the neonatal gut-brain axis, underscoring their importance in infant nutrition and neurodevelopment. Their dual role in shaping the infant gut while influencing brain function presents them as potential game-changers in neonatal health strategies., Competing Interests: The authors declare no conflicts of interest. The authors declare that they have no relevant financial or material interests related to the research described in this article.

Ensuring optimal infant nutrition is crucial for the health and development of children. Many infants aged 0-6 months are fed with infant formula rather than breast milk. Research on cancer cell lines and animal models is limited to examining the nutrition effects of formula and breast milk, as it does not comprehensively consider absorption, metabolism, and the health and social determinants of the infant and its physiology. Our study utilized small intestine organoids induced from human embryo stem cell (ESC) to compare the nutritional effects of breast milk from five donors during their postpartum lactation period of 1-6 months and three types of Stage 1 infant formulae from regular retail stores. Using transcriptomics and untargeted metabolomics approaches, we focused on the differences such as cell growth and development, cell junctions, and extracellular matrix. We also analyzed the roles of pathways including AMPK, Hippo, and Wnt, and identified key genes such as ALPI, SMAD3, TJP1, and WWTR1 for small intestine development. Through observational and in-vitro analysis, our study demonstrates ESC-derived organoids might be a promising model for exploring nutritional effects and underlying mechanisms.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants.

Breastfeeding and human milk are the gold standard for infant feeding. Studying human milk with a systems biology approach in a large longitudinal cohort is needed to understand its complexity and health implications. The Phoenix study is a multicenter cohort study focusing on the interactions of maternal characteristics, human milk composition, infant feeding practices, and health outcomes of Chinese mothers and infants. A total of 779 mother-infant dyads were recruited from November 2021 to September 2022, and 769 mother-infant dyads were enrolled in the study. Scheduled home visits took place at 1, 4, 6, and 12 months postpartum, and 696 dyads (90.5% participants) completed the 12-month visit. At each visit, maternal and infant anthropometry was assessed. Questionnaires were administered to collect longitudinal information on maternal characteristics and lifestyle, infant feeding, and health. Digital diaries were used to record maternal dietary intake, infant feeding, and stool character. Human milk, maternal feces, infant feces, and infant saliva were collected. An external pharmaceutical-level quality assurance approach was implied to ensure the trial quality. Multi-omics techniques (including glycomics, lipidomics, proteomics, and microbiomics) and machine learning algorithms were integrated into the sample and data analysis. The protocol design of the Phoenix study provides a framework for prospective cohort studies of mother-infant dyads and will provide insights into the complex dynamics of human milk and its interplay with maternal and infant health outcomes in the Chinese population.

Postpartum mothers and their healthcare providers often face the challenge of limited data regarding the safety of drug therapies during lactation. Pregnancy can lead to sustained weight gain, and obesity can negatively impact both physical and psychological well-being. The introduction of GLP-1 agonists to augment weight loss has become a topic of interest for many postpartum mothers. Our study aims to investigate the transmission of semaglutide into human milk in the first steps to ensure the safety and health of both lactating mothers and their breastfed infants. Semaglutide quantification was performed using high-resolution liquid chromatography-mass spectrometry. InfantRisk Center Human Milk biorepository released milk samples from eight women collected at 0, 12 and 24 h post-semaglutide administration. Semaglutide was extracted using protein precipitation in methanol, followed by chromatographic separation. Linear calibration curves for the method ranged between 2.5-30 ng/mL, with a limit of detection of 1.7 ng/mL and a limit of quantification of 5.7 ng/mL (LLOQ). Semaglutide was not detected in any of the collected human milk samples. A worst-case scenario of the relative infant dose (RID) was calculated using the LLOQ as the drug concentration in milk when considering semaglutide's bioavailability and long-acting dose profile. The maximum RID projected was 1.26%, far below the standard 10% safety threshold. While questions about long-term infant outcomes, the safety of maternal nutrient intake, and the nutrient content of breast milk remain, our findings suggest that semaglutide concentrations in human milk are unlikely to pose clinical concerns for breastfed infants. These results support healthcare providers in making informed decisions regarding postpartum therapeutic interventions.

Human milk, the gold standard in infant nutrition, is a unique fluid that provides essential nutrients such as lactose, lipids, proteins, and free oligosaccharides. While its primary role is nutritional, it also protects against pathogens. This protection mainly comes from immunoglobulins, with human milk oligosaccharides (HMOs) providing additional support by inhibiting pathogen binding to host cell ligands. The prebiotic and immune-modulatory activity of HMOs strongly depends on their structure. Over 200 individual structures have been identified so far, with the composition varying significantly among women. The structure and composition of HMOs are influenced by factors such as the Lewis blood group, secretor status, and the duration of nursing. HMO profiles are heavily influenced by maternal phenotypes, which are defined based on the expression of two specific fucosyltransferases. However, recent data have shown that HMO content can be modified by various factors, both changeable and unchangeable, including diet, maternal age, gestational age, mode of delivery, breastfeeding frequency, and race. The first part of this overview presents the historical background of these sugars and the efforts by scientists to extract them using the latest chromatography methods. The second part is divided into subchapters that examine modifiable and non-modifiable factors, reviewing the most recent articles on HMO composition variations due to specific reasons and summarizing potential future challenges in conducting these types of studies.

Background: Maternal breast volume is determined by the quantity of glandular and adipose tissue, and it undergoes significant changes during pregnancy. These changes are intricately linked to the development of glandular tissue, which most likely reflects lactation capacity. Evidence indicates that women with overweight or obesity exhibit larger breast volume compared to those with a normal body mass index (BMI), emphasizing the close relationship between breast volume and maternal adiposity. Hence, we aim to investigate breast volume growth and maternal BMI as potential risk factors for low milk production., Methods: Lactating women (n = 609) from the Perth metropolitan area in Western Australia between 2011 and 2023 were included in the analysis. Twenty-four-hour milk production measurements were conducted using the test weighing method, and milk removal frequencies were recorded. Mothers completed questionnaires regarding demographic, obstetric and infant details. Linear and logistic regression models were used to determine maternal and infant factors associated with milk production., Results: Here we show that increasing maternal age and BMI are associated with low milk production. Moreover, larger pre-pregnancy breast volume and breast growth are associated with both higher BMI and milk production., Conclusions: Women who are older, have an obese BMI and who have minimal pre-pregnancy breast volume and breast growth should be provided with antenatal screening and breastfeeding support as they are more likely to experience low milk production.

Human milk (HM) composition, including metabolic hormones and lipids, is influenced by various factors, including lactation stage and, potentially, infant sex, which may affect infant body composition (BC) development. We aimed to: (a) characterize the longitudinal concentration and intake profiles of HM leptin, adiponectin, insulin, and total lipids; (b) determine if their concentrations and intakes differ by infant sex; and (c) explore the intakes relationships with the development of infant BC. Milk samples ( n = 501) were collected from 82 mother-infant dyads during the first 6 months postpartum. Infant 24 h HM intake was measured, and the average cumulative HM component intakes were calculated. The statistical analysis used linear mixed modeling. Intakes of HM leptin, adiponectin, insulin, and total lipids increased to 1 month postpartum and then remained stable. HM intake and total lipids intake but not hormone intakes were positively associated with infant BC (fat-free mass, fat-free mass index, fat mass, fat mass index, percentage fat mass, and fat mass to fat-free mass ratio). HM component concentrations and intakes did not differ by sex. These findings advance our understanding of the temporal nature of HM components, emphasizing the role of infant 24 h HM and total lipids intake in development of infant lean and adipose tissue.

In addition to the numerous immunological and nutritional benefits that breast milk offers to infants, its proportion in the diet must be limited or even excluded in the case of inborn errors of amino acid metabolism (IEM). The objective of the study was to expand knowledge about breastfeeding and the degree of contribution of breast milk to the feeding of infants with IEM before and after the introduction of expanded newborn screening. A retrospective single-centre study was conducted on 127 infants born between 1997 and 2020: 66 with phenylketonuria (PKU), 45 with other IEM (non-PKU), all diagnosed through newborn screening (NBS), and 16 non-PKU diagnosed through selective screening (SS). The time of initiation of dietary treatment and the proportion of breast milk in the diet, both expressed and breastfed, with or without intake control, were analysed at 1, 3, and 6 months after birth. For 47% of the newborns in Groups 1 and 2, the dietary treatment was started before the 10th day of life; in Group 3, the dietary treatment was started after the 10th day of life for all children. During the first month of life, the proportion of infants receiving breast milk was higher in the NBS-PKU (74%) and the NBS non-PKU (80%) groups, compared with 38% in the SS non-PKU infants. In the subsequent months of life, the proportion of infants receiving human milk (either from the breast or a bottle) declined in all groups. This decline occurred more in bottle-fed rather than directly breast-fed infants. Our observations indicate that the model of feeding from a bottle with expressed milk may have had an adverse effect on maintaining lactation and may have contributed to a faster transition to formula milk. Maintaining lactation and extending the period of feeding the infant with human milk in the first 6 months of life is possible by breastfeeding on demand, under regular biochemical monitoring: preferably weekly in PKU infants, and at least every 2-4 weeks in infants with other IEM.

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case-control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at -80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher ( p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher ( p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes' degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP.

The present study examined the fatty acid content of human milk from Polish women living in the Warmia and Mazury region with regard to different lactation periods and compared it with the fatty acid content of selected infant formulas. The analysis included samples of breast milk-colostrum ( n = 21), transitional milk ( n = 26), and mature milk ( n = 22). Fat was extracted using the Rose-Gottlieb method, and the fatty acid profile was determined by gas chromatography with a flame ionization detector (FID). The proportion of SFAs (saturated fatty acids) > MUFAs (monounsaturated fatty acids) > PUFAs (polyunsaturated fatty acids) was determined in each fraction of breast milk and infant formula. Palmitic, oleic, and linoleic acids predominated in breast milk and infant formulas. Colostrum contained lower contents of selected SFAs (caprylic, capric, lauric) and higher contents of selected MUFAs (ercucic) and PUFAs (arachidonic and docosahexaenoic) ( p < 0.05) relative to transitional and mature milk. Infant formulas were distinguished from human milk in terms of their SFA (caproic, caprylic, lauric, arachidic), MUFA (oleic), and PUFA (linoleic, α-linoleic) content. It should be noted that infant formulas contained significantly lower trans fatty acid (TFA) content-more than thirty-six and more than nineteen times lower than in human milk. Furthermore, human milk contained branched-chain fatty acids (BCFAs) at 0.23-0.28%, while infant formulas contained only trace amounts of these acids. The average ratio of n -6 to n -3 fatty acids for human milk was 6.59:1 and was close to the worldwide ratio of 6.53 ± 1.72:1. Both principal component analysis (PCA) and cluster analysis (CA) indicated significant differences in the fatty acid profile relative to lactation and a different profile of infant formulas relative to breast milk.

Lactoferrin (LF) is a major component of human milk. LF supplementation (currently bovine) supports the immune system and helps maintain iron homeostasis in adults. No recombinant human lactoferrin (rhLF) is available for commercial food use. To determine the extent to which rhLF (Effera™) produced by Komagataella phaffii digests similarly to hmLF, a validated in vitro digestion protocol was carried out. Bovine LF (bLF) was used as an additional control, as it is approved for use in various food categories. This study compared the extent of intact protein retention and the profile of peptides released in hmLF, bLF and rhLF (each with low and high iron saturation) across simulated adult gastric and intestinal digestion using gel electrophoresis, ELISA and LC-MS. Intact LF retention across digestion was similar across LF types, but the highest iron-saturated hmLF had greater retention in the simulated gastric fluid than all other sample types. Peptides identified in digested hmLF samples strongly correlated with digested rhLF samples (0.86 < r < 0.92 in the gastric phase and 0.63 < r < 0.70 in the intestinal phase), whereas digested bLF samples were significantly different. These findings support the potential for rhLF as a food ingredient for human consumption.

Breastfeeding is the most important nutrition source for infants. However, managing breastfed infants with signs and symptoms related to food allergy can be difficult. Many studies have shown the presence of different food allergens in breast milk, but the clinical role of these antigens in human milk is still much debated. Milk is the main suspect in exclusively breastfed infants with signs and symptoms attributable to food allergy, even if other foods may be responsible. This narrative review analyzes the recommendations provided by international guidelines to determine the diagnosis and management of IgE-mediated and non-IgE-mediated food allergies in exclusively breastfed infants. Dietary restrictions in lactating mothers of infants with suspected FA are usually not necessary. Only in the very few cases where significant allergy signs and symptoms occur in the infant during exclusive breastfeeding should the lactating mother follow an elimination diet for the suspected food for a short period.

The COVID-19 pandemic has highlighted the role of breastfeeding in providing passive immunity to infants via specific anti-SARS-CoV-2 antibodies in breast milk. We aimed to quantify these antibodies across different lactation stages and identify influencing factors. This prospective study involved mother-child dyads from Innsbruck University Hospital, Austria, with a positive maternal SARS-CoV-2 test during pregnancy or peripartum between 2020 and 2023. We collected breast milk samples at various lactation stages and analyzed anti-Spike S1 receptor-binding domain (S1RBD) immunoglobulins (Ig). Maternal and neonatal data were obtained from interviews and medical records. This study included 140 mothers and 144 neonates. Anti-S1RBD-IgA (72.0%), -IgG (86.0%), and -IgM (41.7%) were highly present in colostrum and decreased as milk matured. Mothers with natural infection and vaccination exhibited higher anti-S1RBD-IgA and -IgG titers in all milk stages. Mothers with moderate to severe infections had higher concentrations of anti-S1RBD-IgA and -IgG in transitional milk and higher anti-S1RBD-IgA and -IgM in mature milk compared to those with mild or asymptomatic infections. Variations in antibody responses were also observed with preterm birth and across different virus waves. This study demonstrates the dynamic nature of breast milk Ig and underscores the importance of breastfeeding during a pandemic., Competing Interests: The authors have no conflicts of interest to declare.

The entero-mammary pathway is a specialized route that selectively translocates bacteria to the newborn's gut, playing a crucial role in neonatal development. Previous studies report shared bacterial and archaeal taxa between human milk and neonatal intestine. However, the functional implications for neonatal development are not fully understood due to limited evidence. This study aimed to identify and characterize the microbiota and metabolome of human milk, mother, and infant stool samples using high-throughput DNA sequencing and FT-ICR MS methodology at delivery and 4 months post-partum. Twenty-one mothers and twenty-five infants were included in this study. Our results on bacterial composition suggest vertical transmission of bacteria through breastfeeding, with major changes occurring during the first 4 months of life. Metabolite chemical characterization sheds light on the growing complexity of the metabolites. Further data integration and network analysis disclosed the interactions between different bacteria and metabolites in the biological system as well as possible unknown pathways. Our findings suggest a shared bacteriome in breastfed mother-neonate pairs, influenced by maternal lifestyle and delivery conditions, serving as probiotic agents in infants for their healthy development. Also, the presence of food biomarkers in infants suggests their origin from breast milk, implying selective vertical transmission of these features., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Several metabolites of the essential amino acid tryptophan have emerged as key players in gut homeostasis through different cellular pathways, particularly through metabolites which can activate the aryl hydrocarbon receptor (AHR). This study aimed to map the metabolism of tryptophan in early life and investigate the effects of specific metabolites on epithelial cells and barrier integrity. Twenty-one tryptophan metabolites were measured in the feces of full-term and preterm neonates as well as in human milk and formula. The ability of specific AHR metabolites to regulate cytokine-induced IL8 expression and maintain barrier integrity was assessed in Caco2 cells and human fetal organoids (HFOs). Overall, higher concentrations of tryptophan metabolites were measured in the feces of full-term neonates compared to those of preterm ones. Within AHR metabolites, indole-3-lactic acid (ILA) was significantly higher in the feces of full-term neonates. Human milk contained different levels of several tryptophan metabolites compared to formula. Particularly, within the AHR metabolites, indole-3-sulfate (I3S) and indole-3-acetic acid (IAA) were significantly higher compared to formula. Fecal-derived ILA and milk-derived IAA were capable of reducing TNFα-induced IL8 expression in Caco2 cells and HFOs in an AHR-dependent manner. Furthermore, fecal-derived ILA and milk-derived IAA significantly reduced TNFα-induced barrier disruption in HFOs.

Breastfeeding is the most appropriate source of a newborn's nutrition; among the plethora of its benefits, its modulation of circadian rhythmicity with melatonin as a potential neuroendocrine transducer has gained increasing interest. Transplacental transfer assures melatonin provision for the fetus, who is devoid of melatonin secretion. Even after birth, the neonatal pineal gland is not able to produce melatonin rhythmically for several months (with an even more prolonged deficiency following preterm birth). In this context, human breast milk constitutes the main natural source of melatonin: diurnal dynamic changes, an acrophase early after midnight, and changes in melatonin concentrations according to gestational age and during the different stages of lactation have been reported. Understudied thus far are the factors impacting on (changes in) melatonin content in human breast milk and their clinical significance in chronobiological adherence in the neonate: maternal as well as environmental aspects have to be investigated in more detail to guide nursing mothers in optimal feeding schedules which probably means a synchronized instead of mistimed feeding practice. This review aims to be thought-provoking regarding the critical role of melatonin in chrononutrition during breastfeeding, highlighting its potential in circadian entrainment and therefore optimizing (neuro)developmental outcomes in the neonatal setting.

One of the most important bioactive components of breast milk are free breast milk oligosaccharides, which are a source of energy for commensal intestinal microorganisms, stimulating the growth of Bifidobacterium , Lactobacillus , and Bacteroides in a child's digestive tract. There is some evidence that maternal, perinatal, and environmental-cultural factors influence the modulation of the breast milk microbiome. This review summarizes research that has examined the composition of the breast milk microbiome and the factors that may influence it. The manuscript highlights the potential importance of the breast milk microbiome for the future development and health of children. The origin of bacteria in breast milk is thought to include the mother's digestive tract (entero-mammary tract), bacterial exposure to the breast during breastfeeding, and the retrograde flow of breast milk from the infant's mouth to the woman's milk ducts. Unfortunately, despite increasingly more precise methods for assessing microorganisms in human milk, the topic of the human milk microbiome is still quite limited and requires scientific research that takes into account various conditions.

Human milk reduces risk for necrotizing enterocolitis in preterm infants. Necrotizing enterocolitis occurs in the ileocecal region where thousands of milk protein-derived peptides have been released from digestion. Digestion-released peptides may exert bioactivity, such as antimicrobial and immunomodulatory activities, in the gut. In this study, we applied mass spectrometry-based peptidomics to characterize peptides present in colostrum before and after in vitro digestion. Sequence-based computational modeling was applied to predict peptides with antimicrobial activity. We identified more peptides in undigested samples, yet the abundances were much higher in the digested samples. Heatmapping demonstrated highly different peptide profiles between undigested and digested samples. Four peptides (α S1 -casein [157-163], α S1 -casein [157-165], β-casein [153-159] and plasminogen [591-597]) were selected, synthesized and tested against common pathogenic bacteria associated with necrotizing enterocolitis. All four exhibited bacteriostatic, though not bactericidal, activities against Klebsiella aerogenes , Citrobacter freundii and Serratia marcescens , but not Escherichia coli .

The correct initial colonization and establishment of the gut microbiota during the early stages of life is a key step, with long-lasting consequences throughout the entire lifespan of the individual. This process is affected by several perinatal factors; among them, feeding mode is known to have a critical role. Breastfeeding is the optimal nutrition for neonates; however, it is not always possible, especially in cases of prematurity or early pathology. In such cases, most commonly babies are fed with infant formulas in spite of the official nutritional and health international organizations' recommendation on the use of donated human milk through milk banks for these cases. However, donated human milk still does not totally match maternal milk in terms of infant growth and gut microbiota development. The present review summarizes the practices of milk banks and hospitals regarding donated human milk, its safety and quality, and the health outcomes in infants fed with donated human milk. Additionally, we explore different alternatives to customize pasteurized donated human milk with the aim of finding the perfect match between each baby and banked milk for promoting the establishment of a beneficial gut microbiota from the early stages of life.

Breast milk contains numerous factors that are involved in the maturation of the immune system and development of the gut microbiota in infants. These factors include transforming growth factor-β1 and 2, immunoglobin A, and lactoferrin. Breast milk factors may also affect epidermal differentiation and the stratum corneum (SC) barrier in infants, but no studies examining these associations over time during infancy have been reported. In this single-center exploratory study, we measured the molecular components of the SC using confocal Raman spectroscopy at 0, 1, 2, 6, and 12 months of age in 39 infants born at our hospital. Breast milk factor concentrations from their mothers' breast milk were determined. Correlation coefficients for the two datasets were estimated for each molecular component of the SC and breast milk factor at each age and SC depth. The results showed that breast milk factors and molecular components of the SC during infancy were partly correlated with infant age in months and SC depth, suggesting that breast milk factors influence the maturation of the SC components. These findings may improve understanding of the pathogenesis of skin diseases associated with skin barrier abnormalities.

Human milk provides essential nutrients for infants but also consists of human milk oligosaccharides (HMOs), which are resistant to digestion by the infant. Bifidobacteria are among the first colonizers, providing various health benefits for the host. This is largely facilitated by their ability to efficiently metabolize HMOs in a species-specific way. Nevertheless, these abilities can vary significantly by strain, and our understanding of the mechanisms applied by different strains from the same species remains incomplete. Therefore, we assessed the effects of strain-level genomic variation in HMO utilization genes on growth on HMOs in 130 strains from 10 species of human associated bifidobacteria. Our findings highlight the extent of genetic diversity between strains of the same species and demonstrate the effects on species-specific HMO utilization, which in most species is largely retained through the conservation of a core set of genes or the presence of redundant pathways. These data will help to refine our understanding of the genetic factors that contribute to the persistence of individual strains and will provide a better mechanistic rationale for the development and optimization of new early-life microbiota-modulating products to improve infant health.

Background: The purpose of this research was to assess the growth, tolerance, and compliance outcomes associated with the consumption of a hydrolyzed rice infant formula (HRF) enriched with 2'-Fucosyllactose (2'-FL) a Human Milk Oligosaccharide (HMO), and nucleotides in an intended population of infants., Methods: This was a non-randomized single-group, multicenter study. The study formula was a hypoallergenic HRF with 2'-FL, Docosahexaenoic acid (DHA), Arachidonic acid (ARA), and nucleotides. Infants 0-90 days of age who were formula fed and experiencing persistent feeding intolerance symptoms, symptoms of suspected food protein (milk and/or soy) allergy, or other conditions where an extensively hydrolyzed infant formula was deemed an appropriate feeding option were recruited by pediatricians from their local populations. The primary outcome was maintenance of weight-for-age z-score. Weight, length, head circumference, formula intake, tolerance measures, clinical symptoms and questionnaires were collected. Thirty-three infants were enrolled, and 27 completed the study, on study product., Results: Weight-for-age z-scores of infants showed a statistically significant improvement from Visit 1 to Visit 4 ( p = 0.0331). There was an adequate daily volume intake of 762 ± 28 mL/day, average daily number of stools of 2.1 ± 0.3, and mean rank stool consistency of 2.38 ± 0.18. After 28 days of switching to a HRF, 86.8 ± 5.9% of the symptoms resolved or got better by Visit 4 as reported by parents., Conclusions: HRF with 2'-FL HMO was safe, well tolerated, and supported weight gain in infants with suspected cow's milk allergy or persistent feeding intolerance.

Growing evidence indicates that human milk oligosaccharides (HMOs) are important bioactive compounds that enhance health and developmental outcomes in breastfed babies. Maternal dietary intake likely contributes to variation in HMO composition, but studies identifying diet-HMO relationships are few and inconsistent. This study aimed to investigate how the maternal intake of macronutrients and micronutrients-specifically proteins, fats, vitamins, and minerals-associated with HMOs at 1 month (n = 210), 6 months (n = 131), and 12 months postpartum (n = 84). Several associations between maternal dietary factors and HMO profiles were identified utilizing partial correlation analysis. For example, maternal free sugar (rho = -0.02, p < 0.01), added sugar (rho = -0.22, p < 0.01), and sugary sweetened beverage (rho = -0.22, p < 0.01) intake were negatively correlated with the most abundant HMO, 2'-fucosyllactose (2'-FL), at 1 month, suggesting that higher sugar consumption was associated with reduced levels of 2'-FL. Further, vitamins D, C, K, and the minerals zinc and potassium were positively correlated with 2'-FL at 1 month (p All < 0.05). For the longitudinal analysis, a mixed-effects linear regression model revealed significant associations between maternal vitamin intake and HMO profiles over time. For example, for each unit increase in niacin intake, there was a 31.355 nmol/mL increase in 2'-FL concentration ( p = 0.03). Overall, the results provide additional evidence supporting a role for maternal nutrition in shaping HMO profiles, which may inform future intervention strategies with the potential of improving infant growth and development through optimal HMO levels in mothers' milk.

The nutrition of preterm infants remains contaminated by wrong beliefs that reflect inexactitudes and perpetuate old practices. In this narrative review, we report current evidence in preterm neonates and in preterm neonates undergoing surgery. Convictions that necrotizing enterocolitis is reduced by the delay in introducing enteral feeding, a slow advancement in enteral feeds, and the systematic control of residual gastric volumes, should be abandoned. On the contrary, these practices prolong the time to reach full enteral feeding. The length of parenteral nutrition should be as short as possible to reduce the infectious risk. Intrauterine growth restriction, hemodynamic and respiratory instability, and patent ductus arteriosus should be considered in advancing enteral feeds, but they must not translate into prolonged fasting, which can be equally dangerous. Clinicians should also keep in mind the risk of refeeding syndrome in case of high amino acid intake and inadequate electrolyte supply, closely monitoring them. Conversely, when preterm infants undergo surgery, nutritional strategies are still based on retrospective studies and opinions rather than on randomized controlled trials. Finally, this review also highlights how the use of adequately fortified human milk is strongly recommended, as it offers unique benefits for immune and gastrointestinal health and neurodevelopmental outcomes.

This scoping review aims to investigate longitudinal changes in minerals and vitamins concentrations in human milk among the Chinese population. Following the PRISMA-ScR guidelines, a comprehensive and systematic literature search was conducted using both English and Chinese databases. Data were extracted and categorized into six defined lactation stages. We found that the concentration of most minerals decreased throughout the lactation period, although calcium (Ca) and magnesium (Mg) fluctuated slightly across lactation periods. Fat-soluble vitamins also showed a decline throughout the lactation period, while water-soluble vitamins exhibited an increasing trend. However, folic acid, biotin, and pantothenic acid demonstrated a downward trend. Overall, this review has identified the longitudinal changes in minerals and vitamins concentrations in human milk among the Chinese population. In order to conduct a more in-depth examination of maternal characteristics and nutritional factors of the composition of human milk, it is recommended to utilize standardized protocols for the collection and analysis of human milk samples.

The optimization of infant neuronal development through nutrition is an increasingly studied area. While human milk consumption during infancy is thought to give a slight cognitive advantage throughout early childhood in comparison to commercial formula, the biological underpinnings of this process are less well-known and debated in the literature. This systematic review seeks to quantitatively analyze whether early diet affects infant neurodevelopment as measured by various neuroimaging modalities and techniques. Results presented suggest that human milk does have a slight positive impact on the structural development of the infant brain-and that this impact is larger in preterm infants. Other diets with distinct macronutrient compositions were also considered, although these had more conflicting results.

Breast milk (BM) plays a crucial role in providing essential fatty acids (FA) and energy for the growing infant. When the mother's own BM is not available, nutritional recommendations suggest donor milk (DM) in clinical and home practices. BM was collected from a variety of donor mothers in different lactation stages. Holder pasteurization (HoP) eliminates potential contaminants to ensure safety. FA content of BM samples from the Breast Milk Collection Center of Pécs, Hungary, were analyzed before and after HoP. HoP decreases the level of C6:0, C8:0, C14:1n-5c, C18:1n-9c, C18:3n-6c, C18:3n-3c, and C20:4n-6c in BM, while C14:0, C16:0, C18:1n-9t, C22:0, C22:1n-9c, C24:0, C24:1n-9c, and C22:6n-3c were found in elevated concentration after HoP. We did not detect time-dependent concentration changes in FAs in the first year of lactation. BM produced for girl infants contains higher C20:2n-6c levels. In the BM of mothers who delivered via cesarean section, C12:0, C15:0, C16:0, C17:0, C18:0, C18:1n-9t, C22:1n-9c levels were higher, while C18:2n-6c, C22:0, C24:0, and C22:6n-3c concentrations were lower compared to mothers who gave birth spontaneously. FAs in BM are constant during the first year of lactation. Although HoP modifies the concentration of different FAs, pasteurized DM provides essential FAs to the developing infant. Current data providing information about the FA profile of BM gives origination to supplementation guidelines.

Milk bioactivity refers to the specific health effects of milk components beyond nutrition. The science of milk bioactivity involves the systematic study of these components and their health effects, as verified by empirical data, controlled experiments, and logical arguments. Conversely, 'faith in milk bioactivity' can be defined as personal opinion, meaning, value, trust, and hope for health effects that are beyond investigation by natural, social, or human sciences. Faith can be strictly secular, but also influenced by spirituality or religion. The aim of this paper is to show that scientific knowledge is frequently supplemented with faith convictions to establish personal and public understanding of milk bioactivity. Mammalian milk is an immensely complex fluid containing myriad proteins, carbohydrates, lipids, and micronutrients with multiple functions across species, genetics, ages, environments, and cultures. Human health includes not only physical health, but also social, mental, and spiritual health, requiring widely different fields of science to prove the relevance, safety, and efficacy of milk interventions. These complex relationships between milk feeding and health outcomes prevent firm conclusions based on science and logic alone. Current beliefs in and understanding of the value of breast milk, colostrum, infant formula, or isolated milk proteins (e.g., immunoglobulins, α-lactalbumin, lactoferrin, and growth factors) show that both science and faith contribute to understand, stimulate, or restrict the use of milk bioactivity. The benefits of breastfeeding for infants are beyond doubt, but the strong beliefs in its health effects rely not only on science, and mechanisms are unclear. Likewise, fear of, or trust in, infant formula may rely on both science and faith. Knowledge from science safeguards individuals and society against 'milk bioactivity superstition'. Conversely, wisdom from faith-based convictions may protect science from unrealistic 'milk bioactivity scientism'. Honesty and transparency about the potentials and limitations of both scientific knowledge and faith convictions are important when informing individuals and society about the nutritious and bioactive qualities of milk.

During lactation, heavy metals and trace elements can be mobilised from the maternal body stores and excreted via human milk. A total of 66 mature human milk samples were collected from lactating women in Latvia between 2016 and 2017 to analyse the content of As, Cd, Pb, Al, Sn, and Ni. Additionally, 50 mature human milk samples were collected between 2022 and 2023 to analyse the content of Cd and Pb. The content of heavy metals and trace elements in human milk was determined using ICP-MS. Only two individual human milk samples contained heavy metals above the method's detection limit-one with an arsenic content of 0.009 mg kg -1 and one with a lead content of 0.047 mg kg -1 . The preliminary data show that human milk among lactating women in Latvia contains only insignificant amounts of heavy metals and trace elements. Concern over such content should not be a reason to choose formula feeding over breastfeeding. Nevertheless, heavy metals, trace elements and other pollutants in human milk should be continuously monitored.

The composition of human breast milk is an ideal combination of substances necessary for the healthy development of an infant's body while protecting from pathogens and the balanced development of the microbiota. Its composition is dynamic and changes with the age of the child, meeting their current needs. The study provides a thorough overview of human milk components, such as immunological components, growth factors, hormones, carbohydrates, lipids, minerals, and vitamins. Authors focus on capturing the most important aspects of the effects of these substances on a newborn's body, while also looking for specific connections and describing the effects on given systems. Supplementation and the use of ingredients are also discussed. The purpose of this paper is to present the current state of knowledge about the bioactive components of human milk and their impact on the growth, development, and health of the young child.

Human milk (HM) contains the essential macronutrients and bioactive compounds necessary for the normal growth and development of newborns. The milk collected by human milk banks is stored frozen and pasteurized, reducing its nutritional and biological value. The purpose of this study was to determine the effect of hyperbaric storage at subzero temperatures (HS-ST) on the macronutrients and bioactive proteins in HM. As control samples, HM was stored at the same temperatures under 0.1 MPa. A Miris HM analyzer was used to determine the macronutrients and the energy value. The lactoferrin (LF), lysozyme (LYZ) and α- lactalbumin ( α- LAC) content was checked using high-performance liquid chromatography, and an ELISA test was used to quantify secretory immunoglobulin A (sIgA). The results showed that the macronutrient content did not change significantly after 90 days of storage at 60 MPa/-5 °C, 78 MPa/-7 °C, 111 MPa/-10 °C or 130 MPa/-12 °C. Retention higher than 90% of LYZ, α- LAC, LF and sIgA was observed in the HM stored at conditions of up to 111 MPa/-10 °C. However, at 130 MPa/-12 °C, there was a reduction in LYZ and LF, by 39 and 89%, respectively. The storage of HM at subzero temperatures at 0.1 MPa did not affect the content of carbohydrates or crude and true protein. For fat and the energy value, significant decreases were observed at -5 °C after 90 days of storage.

In this study, the influence of total sn -2 palmitic triacylglycerols (TAGs) and ratio of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO) in human milk fat substitute (HMFS) on the metabolic changes were investigated in Sprague-Dawley rats. Metabolomics and lipidomics profiling analysis indicated that increasing the total sn -2 palmitic TAGs and OPL to OPO ratio in HMFS could significantly influence glycine, serine and threonine metabolism, glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid metabolism, bile acid biosynthesis, and taurine and hypotaurine metabolism pathways in rats after 4 weeks of feeding, which were mainly related to lipid, bile acid and energy metabolism. Meanwhile, the up-regulation of taurine, L-tryptophan, and L-cysteine, and down-regulations of lysoPC (18:0) and hypoxanthine would contribute to the reduction in inflammatory response and oxidative stress, and improvement of immunity function in rats. In addition, analysis of targeted biochemical factors also revealed that HMFS-fed rats had significantly increased levels of anti-inflammatory factor (IL-4), immunoglobulin A (IgA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px), and decreased levels of pro-inflammatory factors (IL-6 and TNF-α) and malondialdehyde (MDA), compared with those of the control fat-fed rats. Collectively, these observations present new in vivo nutritional evidence for the metabolic regulatory effects of the TAG structure and composition of human milk fat substitutes on the host.

Human milk oligosaccharides (HMOs) are complexes that play a crucial role in shaping the early-life gut microbiota. This study intends to explore whether HMO patterns are associated with the gut microbiota of infants. We included 96 Chinese breastfeeding mother-infant dyads. Breast milk and infant faecal samples were collected and tested. With milk 2'-fucosyllactose, difucosyllactose, and lacto- N -fucopentaose-I as biomarkers, we divided the mothers into secretor and non-secretor groups. HMO patterns were extracted using principal component analysis. The majority (70.7%) of mothers were categorised as secretor and five different HMO patterns were identified. After adjustment, the infants of secretor mothers exhibited a lower relative abundance of Bifidobacterium bifidum (β = -0.245, 95%CI: -0.465~-0.025). An HMO pattern characterised by high levels of 3-fucosyllactose, lacto- N -fucopentaose-III, and lacto- N -neodifucohexaose-II was positively associated with the relative abundance of Bifidobacterium breve ( p = 0.014), while the pattern characterised by lacto- N -neotetraose, 6'-sialyllactose, and sialyllacto- N -tetraose-b was negatively associated with Bifidobacterium breve ( p = 0.027). The pattern characterised by high levels of monofucosyl-lacto- N -hexaose-III and monofucosyl-lacto- N -neohexaose was positively associated with Bifidobacterium dentium ( p = 0.025) and Bifidobacterium bifidum ( p < 0.001), respectively. This study suggests that HMO patterns from mature breast milk were associated with certain gut microbiota of breastfed infants.

An exclusive human milk diet (EHMD) and standardized feeding protocols are two critical methods for safely feeding very low birth weight (VLBW) infants. Our institution initiated a standardized feeding protocol for all VLBW infants in 2018. In this protocol, a human milk fat modular was used only reactively when an infant had poor weight gain, fluid restriction, or hypoglycemia. As part of our NICU quality improvement program, internal utilization review data revealed a potential opportunity to improve growth and reduce costs. While maintaining the EHMD, a simple feeding guideline process change could provide cost savings without sacrificing caloric density or growth. We examined this process change in pre-post cohorts of VLBW infants., Methods: Our revised feeding protocol, established in October 2021, called for a human milk fat modular (Prolact CR) to be added to all infant feeding when parenteral nutrition (PN) and lipids were discontinued. The human milk fat modular concentration is 4 mL per 100 mL feed, providing approximately an additional 2 kcal/oz. We tracked data to compare (1) the use of the human milk fat modular, (2) the use of the human milk +8 fortifier, (3) overall growth before and after feeding protocol changes, and (4) cost differences between protocols., Results: Thirty-six VLBW infants were followed prospectively upon the introduction of the revised feeding protocol. In the revised era, the need for human milk +8 fortifier decreased from 43% to 14%. The decrease in the cost of a more costly fortifier provided a cost savings of USD 2967.78 on average per infant. Overall growth improved from birth to discharge, with severe malnutrition declining from 3.3% to 2.7% and moderate malnutrition declining from 37% to 8%., Conclusions: With the proactive use of a human milk fat modular in a standardized feeding protocol, our VLBW infants showed improved growth, lower malnutrition rates, and decreased use of higher caloric fortifiers.

Human milk oligosaccharides (HMOs) are bioactive factors that benefit neonatal health, but little is known about effects on growth in very preterm infants (<32 weeks' gestation). We aimed to quantify HMO concentrations in human milk fed to very preterm infants during the neonatal hospitalization and investigate associations of HMOs with infant size and body composition at term-equivalent age. In 82 human-milk-fed very preterm infants, we measured HMO concentrations at two time points. We measured anthropometrics and body composition with air displacement plethysmography at term-equivalent age. We calculated means of individual and total HMOs, constructed tertiles of mean HMO concentrations, and assessed differences in outcomes comparing infants in the highest and intermediate tertiles with the lowest tertile using linear mixed effects models, adjusted for potential confounders. The mean (SD) infant gestational age was 28.2 (2.2) weeks, and birthweight was 1063 (386) grams. Exposure to the highest (vs. lowest) tertile of HMO concentrations was not associated with anthropometric or body composition z-scores at term-corrected age. Exposure to the intermediate (vs. lowest) tertile of 3FL was associated with a greater head circumference z-score (0.61, 95% CI 0.15, 1.07). Overall, the results do not support that higher HMO intakes influence growth outcomes in this very preterm cohort.

Human milk promotes the growth of bifidobacteria in the infant gut. Adding bifidobacterial species to infant formula may contribute to increasing their presence in the gut of formula-fed infants. Therefore, the safety and anti-infectious effects of Bifidobacterium breve DSM32583, a breast milk isolate, were assessed in a pilot trial involving 3-month-old infants. The infants were randomly assigned to either the probiotic (PG) or the control (CG) groups. All the infants consumed the same formula, although it was supplemented with the strain (1 × 10 7 cfu/g of formula) in the PG. Overall, 160 infants (80 per group) finished the intervention. Infants in CG gained more weight compared to PG ( p < 0.05), but the weights for age Z-scores at 6 months were within the normal distribution for this age group. The rates of infections affecting the gastrointestinal and respiratory tracts and antibiotic therapy were significantly lower in the PG. The bifidobacterial population and the level of short-chain fatty acids were higher ( p < 0.05) in the fecal samples of PG infants. No adverse events related to formula consumption were observed. In conclusion, the administration of an infant formula with B. breve DSM32583 was safe and exerted potential beneficial effects on gut health.

Human milk oligosaccharides (HMOs) are a set of complex carbohydrates and the third largest solid component of human milk, after lactose and lipids. To date, over 150 HMOs have been identified and the diversity of structures produced by lactating women is influenced by maternal genetics as well as other maternal, infant, and environmental factors. While the concentrations of individual HMOs have been shown to vary between individuals and throughout the course of lactation, the variability of HMO concentration profiles following different pregnancies occurring in the same woman is presently unknown. As such, the objective of this study was to compare HMO concentrations in human milk samples provided by the same women ( n = 34) following repeat pregnancies. We leveraged existing human milk samples and metadata from the UC San Diego Human Milk Research Biorepository (HMB) and measured the concentrations of the 19 most abundant HMOs using high-performance liquid chromatography with fluorescence detection (HPLC-FL). By assessing dissimilarities in HMO concentration profiles, as well as concentration trends in individual structures between pregnancies of each participant, we discovered that HMO profiles largely follow a highly personalized and predictable trajectory following different pregnancies irrespective of non-genetic influences. In conclusion, this is the first study to assess the interactions between parity and time following delivery on variations in HMO compositions.

While direct at-the-breast feeding is biologically optimal, Neonatal Intensive Care Unit (NICU) admission due to infant immaturity or illness often necessitates the expression and storage of parent's milk. The provision of freshly expressed (never stored) parent's own milk to preterm infants is not widely prioritized, and this article provides an exploration of NICU practices and their implications for feeding premature or ill infants with parent's own milk. In this article, we discuss the potential biological benefits of fresh parent's own milk, highlighting its dynamic components and the changes incurred during storage. Research suggests that fresh milk may offer health advantages over stored milk. The authors advocate for further research, emphasizing the need for standardized definitions. Research is needed on the biological impact of fresh milk, both short- and long-term, as well as defining and understanding healthcare economics when using fresh milk.

(1) Background: The aim of the present paper was to study fetal and infant creatine (Cr) supply to improve nutrition and neuroprotection in term and especially in preterm infants. The primary outcomes were the placental Cr flux at the end of pregnancy and the time course of human milk (HM) Cr. (2) Methods: The estimation of placental Cr flux was based on umbilical arterial and venous cord blood Cr in 10 term infants after elective caesarian section. HM Cr, creatinine (Crn), and macronutrients were measured longitudinally in 10 mothers across the first 6 months of breastfeeding. (3) Results: At the end of pregnancy, the mean fetal Cr flux was negative (-2.07 mmol/min). HM Cr was highest in colostrum, decreased significantly within the first 2 weeks of breastfeeding ( p < 0.05), and did not change significantly thereafter. HM Cr was not correlated with HM Crn or macronutrient composition. (4) Conclusions: The present data suggest that fetal endogenous Cr synthesis covers the needs at the end of pregnancy. However, high colostrum Cr and HM Cr levels, independent of macronutrient composition, suggest that there may be a critical Cr demand immediately after birth that needs to be covered by enteral supply.

Limited attention is given to the efficacy of protocols for the estimation of infant intake of milk components when investigating their impact on infant outcomes. We compared the actual measured intake of human milk components with estimations derived from 15 protocols to determine the most reliable approach for estimating intake of HM leptin, adiponectin, insulin, glucose, and total lipid. Twenty mothers who were 3-5 months postpartum completed a 24 h milk profile study with pre-/post-feed milk samples collection. The true infant intake (control group) based on 24 h milk intake (MI) was compared to estimated infant intakes using concentrations from five sampling protocols that were multiplied by one of true infant MI, considered mean MI (800 mL), or global mean MI (766 mL). The mean measured concentrations of six samples (three sets of pre- and post-feed samples, from morning (06:00-09:00), afternoon (13:00-16:00), and evening (19:00-22:00)) multiplied by the true infant MI, mean considered MI, and global mean MI produced the most accurate estimates of infant intake of these components. Therefore, in the absence of 24 h measurements and sampling, a sampling protocol comprising three sets of pre-/post-feed samples provides the most reliable infant intake estimates of HM leptin, adiponectin, insulin, glucose, and total lipid.

The composition of the human milk (HM) microbiota and, consequently, the microorganisms that are passed on to the infant through breastfeeding, can be influenced by various factors such as the mother's health and diet, gestational age, delivery mode, lactation stage, method of infant feeding, and geographical location. The aim of the Human Milk-Gest Study was to compare the microbiota of transient (postpartum 7-15 days) and mature HM (postpartum 45-90 days) of 44 mothers, and to investigate any potential changes associated with preterm birth, mode of delivery, and birth weight in relation to gestational age. The data were classified into five study groups: normal spontaneous delivery-term (NS-T) newborns, cesarean delivery-term (CS-T) newborns, preterm (PT) newborns (with a gestational age of less than 37 weeks), small for gestational age (SGA) newborns, and large for gestational age (LGA) newborns. An analysis of differential abundance was conducted using ANCOM-BC to compare the microbial genera between transient and mature HM samples as well as between other study groups. A significant difference was detected between HM samples at different sampling times and between the study groups ( p < 0.01). In transient HM samples, Ralstonia , Burkholderiaceae&#95;uc , and Pelomonas were significantly dominant in the LGA group compared to the NS-T, CS-T, PT, and SGA groups. In mature HM samples, Burkholderiaceae&#95;uc , Ralstonia , Pelomonas , and Klebsiella were significantly dominant in the LGA group compared to the NS-T, CS-T, and PT groups, while Ralstonia , Burkholderiaceae&#95;uc , and Pelomonas were significantly dominant in the LGA group compared to the SGA group. Differences were also detected between the transient and mature HM samples in the CS-T, PT, SGA, and LGA groups, but no differences occurred in the NS-T groups. In conclusion, we showed that Ralstonia , Burkholderiaceae&#95;uc , and Pelomonas were significantly dominant in the LGA group in transient HM and continued in mature HM. The body mass index (BMI) of the mothers in the LGA group was not >30 at conception, however, the maternal BMI at birth and maternal weight gain during pregnancy were higher than in the other groups. The nutritional composition of HM is specifically designed to meet infant nutritional requirements during early life. Evaluating the effects of HM microbiota on infant microbiota composition and short- and long-term health effects in larger studies would be useful.

(1) Background: Breast milk is the only source of nutrition for breastfed infants, but few studies have examined the relationship between breast milk micronutrients and infant neurodevelopmental outcome in exclusively breastfed infants. The aim of this study was to characterize the association between nicotinamide adenine dinucleotide (NAD)-related compounds in the breast milk of Japanese subjects and infant neurodevelopmental outcome. (2) Methods: A total of 150 mother-child pairs were randomly selected from the three-generation cohort of the Tohoku Medical Megabank in Japan. Infants were exclusively breastfed for up to 6 months. Breast milk was collected at 1 month postpartum, and the quantity of NAD-related substances in the breast milk was quantified. The mothers also completed developmental questionnaires at 6, 12, and 24 months. The relationship between the concentration of NAD-related substances in breast milk and developmental indicators was evaluated via ordinal logistic regression analysis. (3) Results: Nicotinamide mononucleotide (NMN) was quantified as the major NAD precursor in breast milk. The median amount of NMN in the breast milk was 9.2 μM. The NMN concentration in breast milk was the only NAD-related substance in breast milk that showed a significant positive correlation with neurodevelopmental outcome in infants at 24 months. (4) Conclusions: The results suggest that NMN in human milk may be an important nutrient for early childhood development.

Retinol in breast milk is related to plasma concentration among breastfeeding women, but the linear or curvilinear relationships between the two remains unclear. We conducted a cross-sectional study in 403 Chinese breastfeeding women at 42 ± 7 days postpartum. Plasma and breast milk samples were assayed using high performance liquid chromatography to determine the concentration of retinol. Partial Spearman correlation and multivariable fractional polynomial regression were used to examine the relationships between the two retinol concentrations and between plasma retinol concentration and milk-to-plasma (M/P) retinol. The median (interquartile range, IQR) of the retinol concentration in the plasma was 1.39 (1.21, 1.63) μmol/L and 1.15 (0.83, 1.49) μmol/L in the breast milk, respectively. The partial correlation coefficient between them was 0.17 ( p < 0.01). A linear relationship was observed with an adjusted regression coefficient of 0.34 (95% CI: 0.19, 0.49). The relationship between the plasma retinol and M/P ratio was nonlinear and segmented at 1.00 μmol/L of plasma retinol. The regression coefficients, below and above the segmented point, were -1.69 (95% CI: -2.75, -0.62) and -0.29 (95% CI: -0.42, -0.16), respectively. Plasma and breast milk retinol were positively correlated, whereas women with a low concentration of plasma retinol showed a stronger capacity of transferring retinol to breast milk.

Maternal obesity, affecting many pregnant women globally, not only poses immediate health risks but also modulates breast milk composition. Obesity is linked to inflammation and oxidative stress, impacting breast milk's immune properties. This paper explores the intricate relationship between maternal metabolic disorders, such as obesity, and breast milk's immunological components. We conducted a thorough search for original and review articles published until 17 October 2023 in the PUBMED/Scopus database. This search included several terms related to human breast milk, immunological properties, and obesity. Articles were selected with the consensus of all authors. Maternal metabolic disorders have discernible effects on the composition of immune-related components in breast milk, such as immunoglobulins, lactoferrin, leptin, ghrelin, adiponectin, C-reactive protein, growth factors, extracellular vesicles, and lymphocytes. These changes in breast milk composition can significantly impact the newborn's immune system, with potential long-term health implications beyond the immediate postnatal period. Maternal metabolic health is a critical factor in shaping the health trajectory of the neonate through breastfeeding, although the full advantages of breastfeeding for children of mothers with obesity remain uncertain. Ongoing research aims to understand and unravel these links.

Microbiota colonization and development in early life is impacted by various host intrinsic (genetic) factors, but also diet, lifestyle, as well as environmental and residential factors upon and after birth. To characterize the impact of maternal nutrition and environmental factors on vaginally born infant gut microbiota composition, we performed an observational study in five distinct geographical areas in Vietnam. Fecal samples of infants (around 39 days old) and fecal and breast milk samples of their mothers (around 28 years) were collected. The microbiota composition of all samples was analyzed by 16S rRNA gene Illumina sequencing and a bioinformatics workflow based on QIIME. In addition, various breast milk components were determined. Strong associations between the geographically determined maternal diet and breast milk composition as well as infant fecal microbiota were revealed. Most notable was the association of urban Ha Noi with relatively high abundances of taxa considered pathobionts, such as Klebsiella and Citrobacter , at the expense of Bifidobacterium . Breast milk composition was most distinct in rural Ha Long Bay, characterized by higher concentrations of, e.g., docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), selenium, and vitamin B12, while it was characterized by, e.g., iron, zinc, and α-linolenic acid (ALA) in Ha Noi. Breast milk iron levels were positively associated with infant fecal Klebsiella and negatively with Bifidobacterium , while the EPA and DHA levels were positively associated with Bifidobacterium . In conclusion, differences between five regions in Vietnam with respect to both maternal breast milk and infant gut microbiota composition were revealed, most likely in part due to maternal nutrition. Thus, there could be opportunities to beneficially steer infant microbiota development in a more desired (rural instead of urban) direction through the mother's diet.

Infancy is a critical period for neurodevelopment, which includes myelination, synaptogenesis, synaptic pruning, and the development of motor, social-emotional, and cognitive functions. Human milk provides essential nutrients to the infant's developing brain, especially during the first postnatal months. Human milk oligosaccharides (HMOs) are a major component of human milk, and there is growing evidence of the association of individual HMOs with cognitive development in early life. However, to our knowledge, no study has explained these associations with a mechanism of action. Here, we investigated possible mediating associations between HMOs in human milk, brain myelination (measured via myelin water fraction), and measures of motor, language (collected via the Bayley Scales of Infant and Toddler Development (Bayley-III)), and socioemotional development (collected via the Ages and Stages Questionnaire: Social-Emotional Version (ASQ-SE)) in healthy term-born breast-fed infants. The results revealed an association between 6'Sialyllactose and social skills that was mediated by myelination. Furthermore, associations of fucosylated HMOs with language outcomes were observed that were not mediated by myelination. These observations indicate the roles of specific HMOs in neurodevelopment and associated functional outcomes, such as social-emotional function and language development.

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.