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Diarrheal diseases remain the leading cause of high mortality among the infants, particularly in the developing countries; Probiotic intervention for diarrhea has been an ongoing novel approach to diarrheal prevention and treatment. This study aims to characterize immunogenic and probiotic properties of lactic acid bacteria (LAB) isolated from human breast milk and neonates' faeces. The LAB isolates from 16 mothers' breast milk and 13 infants' faeces were screened and identified by 16 S rRNA gene partial sequencing. Their antimicrobial activities against 5 strains of diarrheagenic Escherichia coli were tested. Organic acids production was quantified by HPLC, and antibiotic resistance pattern were determined by VITEK ® . Autoaggregation, co-aggregation and hydrophobicity properties were assessed by UV spectrophotometry and immunomodulatory effect was determined in mouse model. Ninety-three LAB of five genera were identified. The most abundant species was Lactiplantibacillus plantarum with inhibition zones ranged from 8.0 to 25.0 ± 1 mm. Lacticaseibacillus rhamnosus A012 had 76.8 mg/mL lactic acid, (the highest concentration), was susceptible to all antibiotics tested. L. plantarum A011 and L. rhamnosus A012 were highly resistance to gastrointestinal conditions. L. rhamnosus A012 produced hydrophobicity of 25.01% (n-hexadecane), 15.4% (xylene) and its autoaggregation was 32.52%. L. rhamnosus A012 and L. plantarum A011 exert immunomodulatory effects on the cyclophosphamide-treated mice by upregulating anti-inflammatory cytokine and downregulating proinflammatory cytokines. Lactobacillus sp. demonstrated good probiotic and immunomodulatory properties. Further works are ongoing on the practical use of the strains., (© 2024. The Author(s).)

Necrotizing enterocolitis (NEC) is a severe intestinal disease of very preterm infants with mother's own milk (MOM) providing protection, but the contribution of the MOM microbiota to NEC risk has not been explored. Here, we analyze MOM of 110 preterm infants (48 NEC, 62 control) in a cross-sectional study. Breast milk contains viable bacteria, but there is no significant difference in MOM microbiota between NEC and controls. Integrative analysis between MOM microbiota, human milk oligosaccharides (HMOs), and the infant gut microbiota shows positive correlations only between Acinetobacter in the infant gut and Acinetobacter and Staphylococcus in MOM. This study suggests that NEC protection from MOM is not modulated through the MOM microbiota. Thus, "'restoring" the MOM microbiota in donor human milk is unlikely to reduce NEC, and emphasis should instead focus on increasing fresh maternal human milk intake and researching different therapies for NEC prevention., Competing Interests: Declaration of interests L.B. is the UC San Diego Chair of Collaborative Human Milk Research, endowed by the Family Larsson-Rosenquist Foundation (FLRF), Switzerland. L.B. is a co-inventor on patent applications related to the use of HMOs in preventing NEC and other inflammatory diseases. N.D.E. and J.E.B. report grants to their institutions from Prolacta Bioscience US and Danone Early Life Nutrition. N.D.E. declares lecture honoraria donated to charity from Nestlé Nutrition Institute. C.J.S. declares lecture honoraria from Nestlé Nutrition Institute., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The introduction of solid foods to infants, also known as weaning, is a critical point for the development of the complex microbial community inhabiting the human colon, impacting host physiology in infancy and later in life. This research investigated in silico the impact of food-breastmilk combinations on growth and metabolite production by colonic microbes of New Zealand weaning infants using the metagenome-scale metabolic model named Microbial Community. Eighty-nine foods were individually combined with breastmilk, and the 12 combinations with the strongest influence on the microbial production of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were identified. Fiber-rich and polyphenol-rich foods, like pumpkin and blackcurrant, resulted in the greatest increase in predicted fluxes of total SCFAs and individual fluxes of propionate and acetate when combined, respectively, with breastmilk. Identified foods were further combined with other foods and breastmilk, resulting in 66 multiple food-breastmilk combinations. These combinations altered in silico the impact of individual foods on the microbial production of SCFAs and BCFAs, suggesting that the interaction between the dietary compounds composing a meal is the key factor influencing colonic microbes. Blackcurrant combined with other foods and breastmilk promoted the greatest increase in the production of acetate and total SCFAs, while pork combined with other foods and breastmilk decreased the production of total BCFAs.IMPORTANCELittle is known about the influence of complementary foods on the colonic microbiome of weaning infants. Traditional in vitro and in vivo microbiome methods are limited by their resource-consuming concerns. Modeling approaches represent a promising complementary tool to provide insights into the behavior of microbial communities. This study evaluated how foods combined with other foods and human milk affect the production of short-chain fatty acids and branched-chain fatty acids by colonic microbes of weaning infants using a rapid and inexpensive in silico approach. Foods and food combinations identified here are candidates for future experimental investigations, helping to fill a crucial knowledge gap in infant nutrition., Competing Interests: The authors declare no conflict of interest.

The present study aimed to characterize the changes in macromolecular composition and structure in ileal tissue induced by postoperative prolonged starvation (PS), human breast milk feeding (HM) and commercial formula feeding (CF) for 48 and 72 h (h). Forty-two Wistar albino rats underwent an ileal transection and primary anastomosis and were then divided into six subgroups. Two groups of seven rats were food-deprived for 48 and 72 h with free access to water only in metabolic cages (48 h PS, 72 h PS). Then, two groups of seven rats received early enteral trophic nutrition (EEN) either using HM, and CF at 48 h post-operation (48 h HM, 48 h CF). The other two groups of seven rats received the same trophic enteral nutrition at 72 h post-operation (72 h HM, 72 h CF). An additional seven rats were fed normal rat chow (control), after which the ileal tissues were harvested and freeze-dried overnight. Then sample spectra were recorded by Fourier transform infrared (FTIR) spectroscopy. PS at 48 and 72 h resulted in an increase in the concentration of lipids and a decrease in the concentration of proteins. CF and HM trophic feeding induced a decrease in membrane fluidity and an increase in lipid order. Ileal tissues showed similar compositional and structural changes in lipids and proteins in the PS and CF groups after 48 and 72 h. A marked decrease in nucleic acid concentration was seen in CF at 48 h compared to HM. The human milk feeding groups did not induce any significant alterations and showed compositional and structural data similar to the controls. In conclusion, EEN application seems to be safer when introduced at 48 h rather than 72 h and time of this nutrition is crucial to maintain ileum structure and therefore immunity and well-being. HM-induced trophic nutrition is seen to protect the ileal tissue from significant alterations within lipid and protein compositions, whereas CF caused notable changes. HM is absolutely the best nutritional source for gut health in this animal model., (© 2024. The Author(s).)

Breastfeeding provides infection protection for several pathogens but not for noroviruses. Mechanisms explaining this discrepancy have been unclear. In this issue of Cell Host & Microbe, Peiper et al. demonstrate that while breastmilk protects mice from intestinal damage, it promotes neonatal murine norovirus infection due to maternal-derived bile acids. 1 ., Competing Interests: Declaration of interests J.K.P. is on the advisory board of Cell Host & Microbe., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Breast milk is a vital source of nutrients, prebiotics, probiotics, and protective factors, including antibodies, immune cells and antimicrobial proteins. Using bacterial lipopolysaccharide arrays, we investigated the reactivity and specificity of breast milk antibodies towards microbial antigens, comparing samples from rural Kenya and urban Switzerland. Results showed considerable variability in antibody reactivity both within and between these locations. Kenyan breast milk demonstrated broad reactivity to bacterial lipopolysaccharides, likely due to increased microbial exposure. Antibodies primarily recognized the O-antigens of lipopolysaccharides and showed strong binding to specific carbohydrate motifs. Notably, antibodies against specific Escherichia coli O-antigens showed cross-reactivity with parasitic pathogens like Leishmania major and Plasmodium falciparum , thus showing that antibodies reacting against lipopolysaccharide O-antigens can recognize a wide range of antigens beyond bacteria. The observed diversity in antigen recognition highlights the significance of breast milk in safeguarding infants from infections, particularly those prevalent in specific geographic regions. The findings also offer insights for potential immunobiotic strategies to augment natural antibody-mediated defense against diverse pathogens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Crone, Sobek, Müller, Restin, Bassler, Paganini, Zimmermann, Zarnovican, Routier, Romero-Uruñuela, Izquierdo and Hennet.)

Objective: To compare the presence of neutralizing antibodies against SARS-CoV-2 found in the breast milk and blood of vaccinated lactating women with those not vaccinated., Data Source: The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under CRD42021287554 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cohort, case-control, and cross-sectional studies that evaluated antibodies against SARS-CoV-2 in the milk and blood of vaccinated mothers and had as control group unvaccinated mothers were eligible. Health Sciences Descriptors (DeCs), Medical Subject Headings (MeSH) and Emtree descriptors were used for the Virtual Health Library (VHL), Medical Literature Analysis and Retrieval System Online (Medline/Pubmed), and Embase databases, respectively. In the Web of Science and Scopus, the strategy was adapted. No restrictions on the publication period and language were set., Data Synthesis: The search identified 233 records, of which 128 duplicates and 101 papers that did not meet the inclusion criteria were excluded. Hence, four cohort studies were eligible. Nursing mothers vaccinated with the Pfizer-BioNTech and Moderna vaccines showed antibodies against SARS-CoV-2 in their blood and breast milk., Conclusions: Vaccinated lactating women had higher levels of immunoglobulin G (IgG) and A (IgA) in serum and breast milk than unvaccinated women.

Understanding the human milk metabolome can help inform infant nutrition and health. Untargeted metabolomics was used to study breast milk from 31 healthy participants to assess the shared metabolites in milk from participants with various backgrounds and understand how different demographic, health, and environmental factors impact the milk metabolome. Breast milk samples were analyzed by four separate UPLC-MS/MS methods. Metabolite Set Enrichment Analysis was used to study the most and least variable metabolites. The associations between participant factors and the metabolome were assessed with redundancy analyses. Among all 31 participants and between each untargeted UPLC-MS/MS method, 731 metabolites were detected, of which 389 were shared among all participants. Of the shared metabolites, lactose was the least and lactobionate the most variable metabolite. In the biological super pathway analysis, xenobiotics were the most variable metabolites. Infant age, maternal age, number of live births, and pre-pregnancy BMI were associated with the milk metabolome. In conclusion, the most variable metabolites originate from environmental exposures while the well-conserved core metabolites are linked to cell metabolism or are crucial for infant nutrition and osmoregulation. Understanding the variability of the breast milk metabolome can help identify components that are crucial for infant nutrition, growth, and development., (© 2024. The Author(s).)

Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e-118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6'-sialyllactose (P = 2.2e-9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children., (© 2024. The Author(s).)

Background: Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM., Methods: The study was nested within the SYMBA double-blind randomized controlled trial (ACTRN12615001075572), which investigated the effects of maternal prebiotic (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides) supplementation from <21 weeks gestation during pregnancy until 6 months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n = 46) or placebo (n = 54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4, and 6 months., Results: Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. At 2 months, HM of prebiotic-supplemented women had decreased levels of TGF-β1 and TSLP (95% CI: -17.4 [-29.68, -2.28] and -57.32 [-94.22, -4.7] respectively) and increased levels of sCD14 (95% CI: 1.81 [0.17, 3.71]), when compared to the placebo group. At 4 months, IgG1 was lower in the prebiotic group (95% CI: -1.55 [-3.55, -0.12]) compared to placebo group., Conclusion: This exploratory study shows that prebiotic consumption by lactating mothers selectively alters specific immunomodulatory proteins in HM. This finding is crucial for understanding how prebiotic dietary recommendations for pregnant and lactating women can modify the immune properties of HM and potentially influence infant health outcomes through immune support from breastfeeding., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Human milk oligosaccharides (HMOs) are an evolutionarily significant advantage bestowed by mothers for facilitating the development of the infant's gut microbiota. They can avoid absorption in the stomach and small intestine, reaching the colon successfully, where they engage in close interactions with gut microbes. This process also enables HMOs to exert additional prebiotic effects, including regulating the mucus layer, promoting physical growth and brain development, as well as preventing and mitigating conditions such as NEC, allergies, and diarrhea. Here, we comprehensively review the primary ways by which gut microbiota, including Bifidobacteria and other genera, utilize HMOs, and we classify them into five central pathways. Furthermore, we emphasize the metabolic benefits of bacteria consuming HMOs, particularly the recently identified intrinsic link between HMOs and the metabolic conversion of tryptophan to indole and its derivatives. We also examine the extensive probiotic roles of HMOs and their recent research advancements, specifically concentrating on the unsummarized role of HMOs in regulating the mucus layer, where their interaction with the gut microbiota becomes crucial. Additionally, we delve into the principal tools used for functional mining of new HMOs. In conclusion, our study presents a thorough analysis of the interaction mechanism between HMOs and gut microbiota, emphasizing the cooperative utilization of HMOs by gut microbiota, and provides an overview of the subsequent probiotic effects of this interaction. This review provides new insights into the interaction of HMOs with the gut microbiota, which will inform the mechanisms by which HMOs function., (© 2024 Institute of Food Technologists®.)

4-Hydroxychlorothalonil (4-OH CHT), the main metabolite of chlorothalonil and the most widely used fungicide, has been frequently detected in human samples during monitoring. 4-OH CHT may exhibit higher toxicity and persistence in the environment compared to its prototype. In this study, a total of 540 paired serum and breast milk samples from pregnant women in three provinces in China were monitored for contaminant residues. 4-OH CHT was analyzed in the samples using ultra high-performance liquid chromatography - high-resolution mass spectrometry with a detection limit of 20 ng/L. The study investigated the effects of demographic factors, such as BMI, region of residence, and education level, on the levels of 4-OH CHT residues in serum and breast milk. Among the three provinces, the highest median concentration of 4-OH CHT in serum samples was observed in Hebei (1.04 × 10 3  ng/L), while the highest median concentration of 4-OH CHT in breast milk samples was observed in Hubei and Guangdong (491 ng/L). Multiple linear regression was used to investigate the significant positive correlation between 4-OH CHT in serum and breast milk (p = 0.000) after adjusting for personal characteristics. Based on this, the study further explored the influencing factors of transfer efficiencies (TEs) in conjunction with the individual TEs and the personal characteristics of the participants. Our results demonstrated that the age of the volunteers and their exercise habits had an effect on TEs, but further studies are needed to determine whether exercise leads to an increase in TEs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

Background: Late-onset breast milk jaundice (LBMJ) is a common form of hyperbilirubinemia, which can result in serious complications for newborns with persistently high bilirubin levels. The aim of this study was to investigate the differences in fecal metabolites between breastfed infants with and without LBMJ in order to elucidate potential biological mechanisms., Methods: Biological samples were collected from 12 infants with LBMJ and 12 healthy individuals. Ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was utilized for non-targeted determination of fecal metabolites. Principal components analysis (PCA), cluster analysis, and differential metabolite analysis were performed in both positive ion mode and negative ion mode for the two groups. Additionally, the KEGG database was employed to comprehensively analyze the pathways of differential metabolites., Results: There were no significant differences in maternal and neonatal demographic characteristics between the two groups (p > 0.05). The results of PCA and cluster heat map analysis in both modes showed that there were significant differences in metabolites between the two groups. Among 751 differential metabolites (DMs) detected in positive ion mode, 720 were up-regulated in the case group while 31 were down-regulated. In negative ion mode, 1891 DMs were detected, including 817 up-regulated metabolites and 1074 down-regulated metabolites in the case group. Analysis of differential metabolic pathways showed that the DMs of the two groups were mainly annotated and enriched in Biotin metabolism, N-Glycan biosynthesis, Taurine and hypotaurine metabolism, Pyrimidine metabolism, and Pentose and glucuronate interconversions., Conclusion: Significant differences exist in fecal metabolites between LBMJ infants and healthy controls. The study of differential metabolic pathways provides insights into the mechanism of LBMJ., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To enhance health benefits, a probiotic can be co-administered with a metabolizable prebiotic forming a synergistic synbiotic. We assessed the synergies resulting from combining Bifidobacterium longum subsp. infantis LMG 11588 and an age-adapted blend of six human milk oligosaccharides (HMOs) in ex vivo colonic incubation bioreactors seeded with fecal background microbiota from infant and toddler donors. When HMOs were combined with B. infantis LMG 11588, they were rapidly and completely consumed. This resulted in increased short chain fatty acid (SCFA) production compared to the summed SCFA production from individual ingredients (synergy). Remarkably, HMOs were partially consumed for specific infant donors in the absence of B. infantis LMG 11588, yet all donors showed increased SCFA production upon B. infantis LMG 11588 supplementation. We found specific bacterial taxa associated with the differential response pattern to HMOs. Our study shows the importance of carefully selecting pre- and probiotic into a synergistic synbiotic that could benefit infants., (© 2024. The Author(s).)

We discuss the evolution and composition of breast milk and briefly describe how mammalian evolution resulted in lactation, which played a crucial role in infant growth and development. We focus on three teleological factors that significantly contribute to breast milk composition: (1) biological sex at birth, (2) gestational age, and (3) circadian rhythms. We also explain how these factors lead to variability in human milk composition. We emphasize the importance of standardizing the definitions of "preterm" and "term" to accurately study the effects of gestational age on milk composition. Finally, we discuss the role of the circadian clock in regulating lactation and the impact of breast milk on fetal and infant sleep. Investigators may integrate these critical factors when designing a research study that involves the collection of breast milk samples. Teleological factors greatly influence milk composition, and these factors may be considered when designing a study that requires breast milk. We provide both the rationale and application of solutions to address these factors., Competing Interests: Disclosures and Conflicts of InterestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Aims: Human milk (HM) is a complete food that meets the nutritional and energy demands of the newborns. It contains numerous bioactive components, including functional proteins. Variations in HM energy and lipid content have already been reported related to the newborn's sex, but differences between protein profiles are still scarce. This work aimed to identify differences between HM proteins produced by mothers of female and male newborns, in the lactation stages of colostrum and mature milk, and the metabolic pathways involved., Methods: A total of 98 HM samples were collected from 39 lactating women and classified according to the newborn's sex, stages of lactation, and three mothers' age groups, and evaluated about protein concentration and one-dimensional electrophoretic profile. Next, to assess samples with the greatest differences, the HM proteins regarding the newborn's sex and the stages of lactation were compared using nano-LC-MS/MS, in 24 HM samples randomly rearranged into four groups: female and male infants, and colostrum and mature milk. Functional classification, metabolic pathways, and protein interaction networks were analyzed by Gene Ontology, KEGG, and STRING, respectively., Results: The soluble protein content of HM decreased throughout lactation, with differences regarding isolated factors, such as mothers' age group, child's sex and stages of lactation, and also in terms of their interactions. A total of 146 proteins were identified, 42 of which showed different abundances over the sexes of newborns and 53 between the stages of lactation. In general, proteins related to metabolic processes were up-regulated for mothers of male infants and in the mature stage of lactation, while proteins related to defense were up-regulated in mothers of female infants and in the colostrum phase., Conclusion: This study indicated that there are differentiated and specific nutritional and defense needs of newborns, by sex and by lactation phase, which is highly relevant for a more appropriate supply of food to infants receiving HM from donor mothers., (Copyright © 2024. Published by Elsevier Ltd.)

Galectins (Gals), a family of multifunctional glycan-binding proteins, have been traditionally defined as β-galactoside binding lectins. However, certain members of this family have shown selective affinity toward specific glycan structures including human milk oligosaccharides (HMOs) and blood group antigens. In this work, we explored the affinity of human galectins (particularly Gal-1, -3, -4, -7, and -12) toward a panel of oligosaccharides including HMOs and blood group antigens using a complementary approach based on both experimental and computational techniques. While prototype Gal-1 and Gal-7 exhibited differential affinity for type I versus type II Lac/LacNAc residues and recognized fucosylated neutral glycans, chimera-type Gal-3 showed high binding affinity toward poly-LacNAc structures including LNnH and LNnO. Notably, the tandem-repeat human Gal-12 showed preferential recognition of 3-fucosylated glycans, a unique feature among members of the galectin family. Finally, Gal-4 presented a distinctive glycan-binding activity characterized by preferential recognition of specific blood group antigens, also validated by saturation transfer difference nuclear magnetic resonance experiments. Particularly, we identified oligosaccharide blood group A antigen tetraose 6 (BGA6) as a biologically relevant Gal-4 ligand, which specifically inhibited interleukin-6 secretion induced by this lectin on human peripheral blood mononuclear cells. These findings highlight unique determinants underlying specific recognition of HMOs and blood group antigens by human galectins, emphasizing the biological relevance of Gal-4-BGA6 interactions, with critical implications in the development and regulation of inflammatory responses., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Buspirone, an anxiolytic with minimal risk of dependence or respiratory depression, lacks extensive published data on its transfer into human milk during lactation. The objective of this study was to 1) quantify the transfer of buspirone and its active metabolite 1-pyrimidinylpiperazine (1-PP) into human milk, allowing for an estimation of maternal drug exposure to the breastfed infant, and 2) report observations of the infants exposed to buspirone via breastmilk., Methods: Milk samples and health histories were collected from nine lactating mothers who donated milk samples to the InfantRisk Human Milk Biorepository while taking buspirone. The drug concentration-time profile of buspirone and 1-PP was determined using liquid chromatography-mass spectrometry., Results: Buspirone was below the detection level of 1.5 ng/mL in all milk samples with dosages ranging from 7.5 to 30 mg twice daily. However, low levels of active metabolite 1-PP were observed at 7.5 mg twice daily up to 30 mg twice daily. The relative infant dose (RID) calculated ranged from 0.21 to 2.17%, which is below the standard 10% threshold for infant safety. There were no reports of adverse effects in the exposed infants., Conclusion: The levels of buspirone observed in all participants' milk samples were exceedingly low. The subsequently low relative infant dose (RID) in the range of 0.21% to 2.17% is below the 10% threshold for infant safety, suggesting that the transfer of maternal buspirone and its active metabolite (1-PP) into human milk is clinically insignificant and poses minimal risk to a breastfed infant., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the hundreds of bioactive factors in human milk has not been tested. Here, we utilize a cohort of exclusively breastfeeding full-term mother-infant pairs to test for differences in the milk transcriptome and metabolome associated with CMV, and the impact of CMV in breast milk on the infant gut microbiome and infant growth. We find upregulation of the indoleamine 2,3-dioxygenase (IDO) tryptophan-to-kynurenine metabolic pathway in CMV+ milk samples, and that CMV+ milk is associated with decreased Bifidobacterium in the infant gut. Our data indicate two opposing CMV-associated effects on infant growth; with kynurenine positively correlated, and CMV viral load negatively correlated, with infant weight-for-length at 1 month of age. These results suggest CMV transmission, CMV-related changes in milk composition, or both may be modulators of full-term infant development., (© 2024. The Author(s).)

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: Exposure to antigens is crucial for child immune system development, aiding disease prevention and promoting infant health. Some common food antigen proteins are found in human breast milk. However, it is unclear whether gluten antigens linked to celiac disease (CD) are transmitted through breast milk, potentially impacting the development of the infant's immune system., Objective: This study aimed to analyze the passage of gluten immunogenic peptides (GIP) into human breast milk. We evaluated the dynamics of GIP secretion after lactating mothers adopted a controlled gluten-rich diet., Methods: We prospectively enrolled 96 non-CD and 23 CD lactating mothers, assessing total proteins and casein in breast milk, and GIP levels in breast milk and urine. Subsequently, a longitudinal study was conducted in a subgroup of 12 non-CD lactating mothers who adopted a controlled gluten-rich diet. GIP levels in breast milk and urine samples were assayed by multiple sample collections over 96 hours., Results: Analysis of a single sample revealed that 24% of non-CD lactating mothers on a regular unrestricted diet tested positive for GIP in breast milk, and 90% tested positive in urine, with significantly lower concentrations in breast milk. Nevertheless, on a controlled gluten-rich diet and the collection of multiple samples, GIP were detected in 75% and 100% of non-CD participants in breast milk and urine, respectively. The transfer dynamics in breast milk samples were long-enduring and GIP secretion persisted from 0 to 72 h. In contrast, GIP secretion in urine samples was limited to the first 24 h, with inter-individual variations. In the cohort of CD mothers, 82.6% and 87% tested negative for GIP in breast milk and urine, respectively., Conclusions: This study definitively established the presence of GIP in breast milk, with substantial inter-individual variations in secretion dynamics. Our findings provide insights into distinct GIP kinetics observed in sequentially collected breast milk and urine samples, suggesting differential gluten metabolism patterns depending on the organ or system involved. Future research is essential to understand whether GIP functions as sensitizing or tolerogenic agents in the immune system of breastfed infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ruiz-Carnicer, Segura, Moreno, Coronel-Rodríguez, Sousa and Comino.)

Aim: Few studies investigate factors that might influence the content of expressed breastmilk. This study aims to investigate the influence of the intervals between breastmilk pumping and the time of the day on protein and fat concentration in breastmilk., Methods: Mothers of very preterm infants in a neonatal ward who expressed more than 400 mL per day were included. Expressed breastmilk was obtained from each mother over 30 h who were pumping at strictly planned and varying intervals: 2, 3, 4 and 6 h. All samples were analysed using infrared transmission spectroscopy., Results: Ten mothers participated at a median of 22 days postpartum. A total of 176 milk samples were analysed, and the average protein and fat concentrations in g/100 mL were 1.1 ± 0.23 and 4.2 ± 1.3, respectively. The time intervals between breast pumping sessions did not impact protein content, but fat content decreased by longer intervals (p < 0.01). The time of the day for milk pumping did not influence the protein or fat content., Conclusion: A single milk sample collected after any 2-6 h interval, at any time during the day, represents the protein content in the breastmilk, but not the fat content which decreased with longer intervals., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: In lactating women, iodine metabolism is regulated and maintained by the kidneys and mammary glands. Limited research exists on how iodine absorbed by lactating women is distributed between the kidneys and breasts., Objectives: This study aimed to accurately evaluate the total iodine intake (TII), urinary iodine excretion (UIE), and breast milk iodine excretion (BMIE) in lactating women and explore the relationship between TII and total iodine excretion (TIE)., Methods: A 7-d iodine metabolism study was conducted on 41 lactating women with a mean age of 30 y in Yuncheng and Gaoqing, China, from December 2021 to August 2023. TII and TIE were calculated by measuring the iodine content in food, water, 24-h urine, feces, and breast milk. The urinary iodine excretion rate (UIER), breast milk iodine excretion rate (BMIER), and partitioning of iodine excretion between urine and breast milk were determined., Results: Iodine metabolism studies were performed for 285 d. The median TII and TIE values were 255 and 263 μg/d, respectively. With an increase in TII, UIER, and BMIER, the UIE and BMIE to TII ratio exhibited a downward trend. The median UIER, BMIER, and proportion of iodine excreted in urine and breast milk were 51.5%, 38.5%, 52%, and 37%, respectively. When the TII was <120 μg/d, the BMIER decreased with the increase of the TII (β: -0.90; 95% confidence interval: -1.08, -0.72)., Conclusions: When maternal iodine intake is low, the proportion in breast milk increases, ensuring sufficient iodine nutrition for infants. In addition, the UIE of lactating women with adequate iodine concentrations is higher than their BMIE. This study was registered at clinicaltrials.gov as NCT04492657., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Human milk oligosaccharides (HMOs) are a structurally complex group of unbound polysaccharides, representing the third-largest solid component in breast milk. They play a crucial role in the intestinal health and immune system development of infants. Sialylated HMOs, including 3'-sialactose (3'-SL) and 6'-sialactose (6'-SL), are major components of HMOs, playing significant roles in immune regulation, anti-inflammatory processes, and promotion of probiotic growth. Currently, the cost-effective production of high-value sialactose by microbial fermentation with readily available raw materials has become a research hotspot due to the high nutritional value and potential applications of sialylated HMOs in infant food. This paper summarizes the functions and biosynthesis of 3'-SL and 6'-SL. Furthermore, it reviews the research progress in the synthesis of sialactose by Escherichia coli , offering valuable insights for future industrial production.

Groundwater arsenic poisoning has posed serious health hazards in the exposed population. The objective of the study is to evaluate the arsenic ingestion from breastmilk among pediatric population in Bihar. In the present study, the total women selected were n = 513. Out of which n = 378 women after consent provided their breastmilk for the study, n = 58 subjects were non-lactating but had some type of disease in them and n = 77 subjects denied for the breastmilk sample. Hence, they were selected for the women health study. In addition, urine samples from n = 184 infants' urine were collected for human arsenic exposure study. The study reveals that the arsenic content in the exposed women (in 55%) was significantly high in the breast milk against the WHO permissible limit 0.64 µg/L followed by their urine and blood samples as biological marker. Moreover, the child's urine also had arsenic content greater than the permissible limit (< 50 µg/L) in 67% of the studied children from the arsenic exposed regions. Concerningly, the rate at which arsenic is eliminated from an infant's body via urine in real time was only 50%. This arsenic exposure to young infants has caused potential risks and future health implications. Moreover, the arsenic content was also very high in the analyzed staple food samples such as rice, wheat and potato which is the major cause for arsenic contamination in breastmilk. The study advocates for prompt action to address the issue and implement stringent legislative measures in order to mitigate and eradicate this pressing problem that has implications for future generations., (© 2024. The Author(s).)

Breastfeeding and microbial colonization during infancy occur within a critical time window for development, and both are thought to influence the risk of respiratory illness. However, the mechanisms underlying the protective effects of breastfeeding and the regulation of microbial colonization are poorly understood. Here, we profiled the nasal and gut microbiomes, breastfeeding characteristics, and maternal milk composition of 2,227 children from the CHILD Cohort Study. We identified robust colonization patterns that, together with milk components, predict preschool asthma and mediate the protective effects of breastfeeding. We found that early cessation of breastfeeding (before 3 months) leads to the premature acquisition of microbial species and functions, including Ruminococcus gnavus and tryptophan biosynthesis, which were previously linked to immune modulation and asthma. Conversely, longer exclusive breastfeeding supports a paced microbial development, protecting against asthma. These findings underscore the importance of extended breastfeeding for respiratory health and highlight potential microbial targets for intervention., Competing Interests: Declaration of interests M.B.A. receives research funding from the Canadian and US governments, the Bill and Melinda Gates Foundation, and the Garfield Weston Foundation. She holds a Canada Research Chair in Early Nutrition and the Developmental Origins of Health and Disease and is a fellow of the CIFAR Humans and the Microbiome program. She has consulted for DSM Nutritional Products, serves on the scientific advisory board for TinyHealth, and has received speaking honoraria from Prolacta Biosciences. She has contributed without remuneration to online courses on breast milk and the infant microbiome produced by Microbiome Courses. L.B. receives research funding from the United States National Institutes of Health and the Bill and Melinda Gates Foundation. L.B. is the UC San Diego Chair of Collaborative Human Milk Research endowed by the Family Larsson-Rosenquist Foundation in Switzerland. V.B. is currently an employee of F. Hoffman-La Roche Ltd.; however, the published work was done prior to her employment and does not involve/promote any of Roche’s materials or point of view., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Human breast milk is the optimal source of nutrition for newborns, but the potential transfer of contaminants like mycotoxins, particularly ochratoxin A (OTA), from maternal blood to milk remains a concern. This systematic review aims to provide a comprehensive analysis of global OTA levels in human breast milk and assess the associated health risks. We conducted a thorough search of scientific databases, including Web of Science, ScienceDirect, Scopus, Google Scholar and PubMed, using keywords related to OTA in human breast milk. A total of 39 studies met the inclusion criteria for this review. OTA levels compared to limits, estimated infant intake at various ages and health risks assessed using Margin of Exposures (MOEs) and Hazard quotient (HQ). Our findings reveal the widespread presence of OTA in breast milk across different regions, with notably higher levels detected in Africa compared to Asia, South America and Europe. The higher concentrations observed in warmer, humid climates suggest that environmental factors significantly influence OTA contamination. Mature breast milk samples generally exhibited greater OTA exposure. The neoplastic and non-neoplastic effects demonstrate generally low risks globally. The regional differences in OTA levels and associated health risk assessments underscore the need for continued research into the health impacts of OTA exposure in infants. This includes further investigation into multiple sources of exposure, such as infant formula, within the broader context of the exposome framework.

Objective: In this pilot study, we verified safe practices for breast milk expression, storage, and duration, based on bacteriological results., Results: We collected breast milk samples from three healthy lactating volunteers and analyzed the bacterial flora and changes in the viable bacterial counts (including those of Staphylococcus) of the samples. Although no consistent change could be observed in the abundance of a particular bacterial group in samples expressed under hygienic control conditions, viable bacterial counts were higher in self-expressed milk than in milk expressed under hygienic control conditions. In conclusion, increased hygiene awareness is vital during breast milk expression and storage., (© 2024. The Author(s).)

Mother's milk contains diverse bacterial communities, although their impact on microbial colonization in very-low-birth-weight (VLBW, <1,500 g) infants remains unknown. Here, we examine relationships between the microbiota in preterm mother's milk and the VLBW infant gut across initial hospitalization (n = 94 mother-infant dyads, 422 milk-stool pairs). Shared zero-radius operational taxonomic units (zOTUs) between milk-stool pairs account for ∼30%-40% of zOTUs in the VLBW infant's gut. We show dose-response relationships between intakes of several genera from milk and their concentrations in the infant's gut. These relationships and those related to microbial sharing change temporally and are modified by in-hospital feeding practices (especially direct breastfeeding) and maternal-infant antibiotic use. Correlations also exist between milk and stool microbial consortia, suggesting that multiple milk microbes may influence overall gut communities together. These results highlight that the mother's milk microbiota may shape the gut colonization of VLBW infants by delivering specific bacteria and through intricate microbial interactions., Competing Interests: Declaration of interests E.M.C. acknowledges research support from Lallemand Health Solutions and Ocean Spray and consultant fees, speaker, and/or travel support from Danone, Nestlé, and Lallemand Health Solutions. P.M.S. is a stockholder and an advisory board member for Antibe Therapeutics Inc. A.S. is a co-founder of MedBiome, a clinical microbiomics company., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus found in human breast milk that is frequently transmitted from HCMV-seropositive mothers to their infants during the postnatal period. Despite extensive research, the mechanisms underlying HCMV transmission from breast milk and the anatomical location at which virus transfer takes place remain unclear. Breast milk contains many uniquely differentiated macrophages that undergo specific morphological and functional modifications in the mammary gland during lactation. Although the existence of permissive HCMV infection in differentiated macrophages has been well-described, the role of breast milk in this process remains unknown. Herein, we report that exposure of isolated peripheral blood monocytes to breast milk induces their differentiation into macrophages that exhibit an M2 phenotype (CD14 high CD163 high CD68 high CD206 high ) and promotes a productive and sustained HCMV infection. We also found that breast milk triggers macrophage proliferation and thus sustains a unique population of proliferating, long-lived, and HCMV-susceptible macrophages that are capable of ongoing production of infectious virions. These results suggest a mechanism that explains chronic HCMV shedding into the breast milk of postpartum seropositive mothers. We also found that HCMV virions released from breast milk-induced macrophages generate a productive infection in primary infant tonsil epithelial cells. Collectively, our results suggest that breast milk may facilitate HCMV transmission from mother to infant via the oropharyngeal mucosa., Importance: While human cytomegalovirus (HCMV) is frequently detected in the breast milk of HCMV-seropositive women and is often transmitted to infants via breastfeeding, the mechanisms by which this transmission occurs remain unclear. In this study, we modeled HCMV transmission at the oropharyngeal mucosa. We treated human monocytes with breast milk to mimic the lactating mammary gland microenvironment. We found that monocytes differentiated into macrophages with an M2 phenotype, which were highly permissive for HCMV. We also discovered that breast milk induces macrophage proliferation. Thus, exposure to breast milk increased the number of HCMV-susceptible macrophages and supported high levels of infectious HCMV. We found that HCMV virions released from breast milk-induced macrophages could infect primary infant tonsil epithelial cells. Collectively, these findings reveal the dual role of breast milk that induces the differentiation and proliferation of macrophages in the mammary gland and thus facilitates mother-to-child HCMV transmission at the oropharyngeal mucosa., Competing Interests: The authors declare no conflict of interest.

Introduction: Managing burn injuries is a challenge in healthcare. Due to the alarming increase in antibiotic resistance, new prophylactic and therapeutic strategies are being sought. This study aimed to evaluate the potential of live Lactic Acid Bacteria for managing burn infections, using Galleria mellonella larvae as an alternative preclinical animal model and comparing the outcomes with a common antibiotic., Methods: The antimicrobial activity of LAB isolated from human breast milk was assessed in vitro against Pseudomonas aeruginosa ATCC 27853. Additionally, the immunomodulatory effects of LAB were evaluated in vivo using the G. mellonella burn wound infection model., Results and Discussion: In vitro results demonstrated the antimicrobial activity of Lactic Acid Bacteria against P. aeruginosa . In vivo results show that their prophylactic treatment improves, statistically significant, larval survival and modulates the expression of immunity-related genes, Gallerimycin and Relish/NF-κB, strain-dependently. These findings lay the foundation and suggest a promising alternative for burn wound prevention and management, reducing the risk of antibiotic resistance, enhancing immune modulation, and validating the potential G. mellonella as a skin burn wound model., Competing Interests: Authors NV, MC, IM, LP, FV, SD, GSc, GP and RM were NATIVAL s.r.l. founders at the time of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guarnieri, Venditti, Cutuli, Brancazio, Salvatore, Magnifico, Pietrangelo, Falcone, Vergalito, Nicolosi, Scarsella, Davinelli, Scapagnini, Petronio Petronio and Di Marco.)

Background: When sufficient maternal milk is not available, donor human milk or formula are the alternative forms of enteral nutrition for very preterm or very low-birthweight (VLBW) infants. Donor human milk may retain the non-nutritive benefits of maternal milk and has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or VLBW infants., Objectives: To assess the effectiveness of donor human milk compared with formula for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants when sufficient maternal milk is not available., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care (MIC) database, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to February 2024. We searched clinical trials registries and examined the reference lists of included studies., Selection Criteria: Randomised or quasi-randomised controlled trials comparing feeding with donor human milk versus formula in very preterm (< 32 weeks' gestation) or VLBW (< 1500 g) infants., Data Collection and Analysis: Two review authors evaluated the risk of bias in the trials, extracted data, and synthesised effect estimates using risk ratio, risk difference, and mean difference, with associated 95% confidence intervals. The primary outcomes were NEC, late-onset invasive infection, and all-cause mortality before hospital discharge. The secondary outcomes were growth parameters and neurodevelopment. We used the GRADE approach to assess the certainty of the evidence for our primary outcomes., Main Results: Twelve trials with a total of 2296 infants fulfilled the inclusion criteria. Most trials were small (average sample size was 191 infants). All trials were performed in neonatal units in Europe or North America. Five trials were conducted more than 40 years ago; the remaining seven trials were conducted in the year 2000 or later. Some trials had methodological weaknesses, including concerns regarding masking of investigators and selective reporting. Meta-analysis showed that donor human milk reduces the risk of NEC (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.37 to 0.76; I² = 4%; risk difference (RD) -0.03, 95% CI -0.05 to -0.01; 11 trials, 2261 infants; high certainty evidence). Donor human milk probably has little or no effect on late-onset invasive infection (RR 1.12, 0.95 to 1.31; I² = 27%; RD 0.03, 95% CI -0.01 to -0.07; 7 trials, 1611 infants; moderate certainty evidence) or all-cause mortality (RR 1.00, 95% CI 0.76 to 1.31; I² = 0%; RD -0.00, 95% CI -0.02 to 0.02; 9 trials, 2116 infants; moderate certainty evidence)., Authors' Conclusions: The evidence shows that donor human milk reduces the risk of NEC by about half in very preterm or VLBW infants. There is probably little or no effect on late-onset invasive infection or all-cause mortality before hospital discharge., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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.

Background: Mother's milk provides optimal nutrition for infants. Donor human milk (DHM) is recommended for low birthweight infants when mother's milk is unavailable. Little is known about human milk (HM) donation practices in New Zealand (NZ), where few HM banks are available. This study aimed to investigate parents' and health professionals' (HP) experiences with formal and informal HM donation in NZ., Methods: Two electronic surveys were disseminated in 2022 to parents and HPs involved with HM donation in NZ. The surveys covered respondents' views and experiences with HM donation. HPs were also asked about HM donation practices in their workplace. Chi-squared and Fisher-Freeman-Halton exact tests were used for quantitative analysis and qualitative data were thematically analysed using inductive approach., Results: A total of 232 HP and 496 parents completed the surveys. Most parents either donated (52%) or sought DHM (26%) for their infant and most donations were informal, arranged between individuals (52%) or through hospital staff (22%). HP reported DHM was used in 86% of facilities, with only 20% of donations facilitated by HM banks. Almost half (48%) of HP stated they would like to use DHM in their workplace but access was limited. The most common screening processes undertaken by parents and HP before informal HM donation were lifestyle including smoking status, medication, drug and alcohol intake (44% and 36%, respectively) and serological screening such as CMV, HIV, Hepatitis C or B (30% and 39%, respectively). Pasteurisation of DHM obtained informally was not common. Most donors were satisfied with their HM donation experiences (informal and/or formal, 91%) and most respondents supported use of DHM in hospitals and community. Participants reported HM donation could be improved (e.g., better access) and identified potential benefits (e.g., species-specific nutrition) and risks (e.g., pathogens) for the infant. Potential benefits for the donor were also identified (e.g., altruism), but respondents acknowledged potential negative impacts (e.g., cost)., Conclusion: Informal HM donation in NZ is common. Most parents and HP support the use of DHM; however, improvements to current practices are needed to ensure safer and more equitable access to DHM., (© 2024. The Author(s).)

Considering the current level of chemical and biological synthesis technology, it was a sensible selection to obtain milk oligosaccharides (MOs) from other mammals as the potential substitute for human MOs (HMOs) that possessed various structural features in the infant formula. Through a comprehensive analysis of the content, structure, and function of MOs in six distinct varieties of mammal milk, it has been shown that goat milk was the most suitable material for the preparation as a human milk substitute. Goat MOs (GMOs) had a relatively high content and diverse structural features compared to those found in other mammalian milks. The concentration of GMOs in colostrum ranged from 60 to 350 mg/L, whereas in mature milk, it ranged from 200 to 24,00 mg/L. The acidic oligosaccharides in goat milk have attracted considerable attention due to their closeness in acidic content and structural diversity with HMOs. Simultaneously, it was discovered that some structures, like N-glycolylneuraminic acid, were found to have a certain content in GMOs and served essential functional properties. Moreover, studies focused on the extraction of MOs from goat milk indicated that the production of GMOs on an industrial scale was viable. Furthermore, it is imperative to do further study on GMOs to enhance the preparation process, discover of new MOs structures and bioactivity evaluation, which will contribute to the development of both the commercial production of MOs and the goat milk industry., (© 2024 Institute of Food Technologists®.)

Abstract Background: To detect the presence of botulinum toxin in breast milk from lactating subjects treated with facial botulinum toxin injections, as measured by enzyme-linked immunosorbent assay (ELISA). Objective: For this pilot study, lactating women were injected with standardized facial botulinum toxin type A (BTXA) (range 40-92 U). Collected breast milk samples over 5 days were analyzed for the presence of botulinum toxin. Exclusion criteria included (1) lactating women still using their breast milk for their infant, (2) muscular disorders, (3) any medication that could interfere with neuromuscular function, (4) uncontrolled systemic disease, (5) pregnant, and (6) neuromodulator injection in the past 90 days. Methods: For this pilot study, lactating women were injected with standardized facial botulinum toxin type A (BTXA) (range 40-92 U). Collected breast milk samples over 5 days were analyzed for the presence of botulinum toxin. Exclusion criteria included (1) lactating women still using their breast milk for their infant, (2) muscular disorders, (3) any medication that could interfere with neuromuscular function, (4) uncontrolled systemic disease, (5) pregnant, and (6) neuromodulator injection in the past 90 days. Results: Four lactating women were recruited. Eight samples had no BTXA detected, whereas 8 of the 16 total had detectible amounts, which were well below the reported lethal oral dose for an infant. Conclusion: Although the exclusion of lactating women from receiving cosmetic botulinum toxin injections is out of an abundance of caution to the theoretical risk to the infant, this study helps support the notion that facial botulinum toxin injections do not warrant an interruption in breastfeeding. Further studies with larger sample sizes are needed.

Purpose: The World Health Organization's International Agency on Research for Cancer has determined that glyphosate is "probably carcinogenic to humans." There is a great public interest to investigate whether glyphosate are detected in breast milk. Thus, the goal of this study was to assess the concentration of glyphosate and its main metabolite in breast milk. Materials and Methods: Liquid chromatography was performed at 25°C using a Luna NH 2 , 50 × 2 mm, 3⎛ m (Phenomenex) analytical column. Electrospray ionization mass spectrometry was collected using negative ionization mode. The calibration curve for glyphosate ranged from 10 to 250 ng/mL. The detection limit was 1 ng/mL. Results: Breast milk samples were collected from 74 women, which included vegans ( n = 26), vegetarians ( n = 22), and nonvegetarians ( n = 26). One of the 74 milk samples contained a detectable concentration of glyphosate and an additional 7 were found to contain aminomethylphosphonic acid. Conclusions: In breast milk samples collected mainly from women residing in urban regions of the United States, glyphosate detection was rare. Consistently, breastfed infants have a low or minimal risk of being exposed to glyphosate through ingestion of mother's milk. It is possible that the presence/absence and/or level of concentration of milk glyphosate depend on a place of residency and time of breastfeeding vis-à-vis time of its agricultural application.

Clinicians caring for small, vulnerable newborns increasingly have access to specific nutritional information about human milk through point-of-care analyzers and labeled products. It is critical for clinicians to recognize that there is considerable variability in how human milk nutritional data are derived and reported, which impacts the interpretation of nutritional values, comparison of nutritional data between products, and ultimately the ability to deliver optimal nutritional care. This article distills key issues that will enable clinicians to interpret human milk nutritional labels/analysis more effectively, ultimately allowing them to make better decisions about dietary strategies. We aim to empower clinicians to ask questions about milk sampling techniques, reported nutrient values, analysis techniques, and milk bank pooling practices. This knowledge can put human milk nutrient values in context, improve clinical care, and help to drive more rigorous research for exploring the impact of human milk feeding on infant outcomes., (© 2024. The Author(s).)

Background: Concentrations of vitamin D (VitD) and 25-hydroxyvitamin D (25OHD) in breastmilk are low despite the essential role of VitD for normal infant bone development, yet additional metabolic forms of vitamin D may be present. This study evaluates the contribution of sulfated vitamin D metabolites, vitamin D 3 -sulfate (VitD 3 -S) and 25-hydroxyvitamin D 3 -sulfate (25OHD 3 -S) for lactating women and assesses the response to high-dose VitD 3 supplementation., Methods: Serum and breastmilk were measured before and after 28 days with 5000 IU/day VitD 3 intake in 20 lactating women. Concentrations of VitD 3 -S and 25OHD 3 -S in milk, and 25OHD 2 , 25OHD 3 , 25OHD 3 -S, VitD 3 and VitD 3 -S in serum were determined by mass spectrometry., Results: Baseline vitamin D status was categorized as sufficient (mean ± SD serum 25OHD 3 69 ± 19 nmol/L), and both serum VitD 3 and 25OHD 3 increased following supplementation (p < 0.001). 25OHD 3 -S was 91 ± 19 nmol/L in serum and 0.47 ± 0.09 nmol/L in breastmilk. VitD 3 -S concentrations were 2.92 ± 0.70 nmol/L in serum and 6.4 ± 3.9 nmol/L in breastmilk. Neither sulfated metabolite significantly changed with supplementation in either serum or breastmilk., Conclusions: Sulfated vitamin D metabolites have prominent roles for women during lactation with 25OHD 3 -S highly abundant in serum and VitD 3 -S distinctly abundant in breastmilk. These data support the notion that 25OHD 3 -S and VitD 3 -S may have physiological relevance during lactation and nutritional usage for nursing infants., Competing Interests: Conflict of interest The authors have no commercial or financial conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Mother's Own Milk (MOM) reduces the risk of complications in premature infants. Breastfeeding rates for late preterm and term infants in the neonatal intensive care unit (NICU) are significantly lower than that of breastfed healthy term newborns at 6 months of age., Design: This was a retrospective cohort study of neonates born at 34 weeks 0 days or later. Infants who were directly breastfed in the NICU and were discharged on breast milk were included. Logistic regression modeling was used to determine the significance of association., Results: 171 mother-infant dyads were included. After adjusting for confounders, the number of breastfeeding attempts during the NICU stay was significantly associated with the availability of MOM at six months of age (p = 0.003, 95% CI 1.02 to 1.14)., Conclusion: This study is the first to show an association between the number of direct breastfeeding attempts in the NICU and availability of MOM at six months of age., (© 2024. The Author(s).)

Background: Bereaved mothers describe positive experiences donating breast milk and negative experiences when not informed of opportunities to donate. Predictors of whether mothers donate milk are unknown, impairing efforts to optimize support in completing donation. Objective: To define circumstances associated with completing mother's milk (MM) donation during bereavement. Methods: A retrospective cohort study included dyads of bereaved mothers and their deceased children if a child's death occurred on-site at a quaternary care children's hospital during 2016-2020, the child had documentation of MM availability, and age at death <24 months. The primary outcome was the completion of MM donation to the milk bank. Multivariate logistic regression measured associations between clinical variables and odds of completion. Results: Of 124 deceased children with documented MM exposure, 34 mothers (28%) of 35 of those children completed MM donation, donating a mean of 13.7 liters (SD 16.8). The child's race/ethnicity documented in the medical record was White for 25 (71%), Black/African American (AA) for 1 (3%), Asian for 1 (3%), and Hispanic/Latino for 8 (23%). Referenced to mothers of White children, being a mother of an AA [OR 0.05 (95% CI: 0.01-0.43)] or Asian [0.08 (0.01-0.75)] child was associated with lower odds of donation. Referenced to mothers delivering full term (≥37 weeks'), mothers delivering <34 weeks showed higher odds [5.0 (1.5-17.5)] of donation. Conclusion: Relatively few bereaved mothers of children with indicators of MM exposure completed donation. The results suggest an opportunity to ensure bereaved mothers are uniformly informed and supported in donating.

Objective: In 2017, our Level IV NICU switched from providing bovine-derived (BOV-fort) to human milk-derived fortifiers (HM-fort) and donor human milk (DHM) to premature infants born ≤ 30 weeks or ≤1250 g. Following this change, providers anecdotally observed increased hypoglycemia, hypercalcemia, and hyperphosphatemia. This study investigated potential laboratory differences between infants fed Bovine vs. Human milk derived fortifier., Methods: Lab measurements from 402 infants (232 BOV-fort, 170 HM-fort) born between 2015 and 2019 were compared between groups., Results: The proportion of infants ever having a blood glucose ≤ 45 mg/dL (p < 0.0001) was higher in the HM-fort group. The proportion of infants ever experiencing a phosphorus > 8.0 mg/dL were higher in the HM-fort group (p < 0.0001). The proportion of infants ever experiencing calcium > 11.4 mg/dL was higher in the HM-Fort group (p = 0.019)., Conclusions: Provision of HM-Fort and DHM to extremely premature infants is associated with metabolic derangements., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Breast milk confers multiple benefits to the neonate, including passive immunity against multiple microorganisms via Abs. However, it remains unclear whether breast milk-derived Abs affect vaccine-induced immunity in the neonate. We evaluated in C57BL/6 and BALB/c mice whether breastfeeding from an mRNA-SARS-CoV-2-vaccinated dam affects vaccine-induced immunity in neonate mice. Using an experimental model that allows the distinction of maternal Abs and neonate Abs based on their allotype, we show that breastfeeding from an immune dam is associated with reduced vaccine immunity in the neonate. Importantly, mice that breastfed from an immune dam showed reduced numbers of plasma cells after vaccination, relative to mice that breastfed from a naive dam. Our subsequent studies using an mRNA-luciferase reporter system show that passive transfer of Abs through breastfeeding accelerates the clearance of vaccine Ag in suckling mice, resulting in reduced Ag availability. Altogether, maternal Abs transferred through breast milk can protect against infectious microorganisms, but they may also interfere with the neonate's response to vaccination by accelerating the clearance of vaccine Ag. These findings are important for understanding the effects of maternal Abs on the neonate's response to vaccines and may provide insights for improving neonatal vaccines., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Breast milk is a vital source of nutrition for breastfed infants, providing essential nutrients and elements but, in some cases, toxic ones. This is the first case-control study that investigated the elemental profile of breast milk samples collected from mothers residing in Matiari (Sindh), a region with insufficient industrial waste management, and its potential impact on infants' anthropometrics. Precisely, 62 milk samples, including 42 cases and 20 controls, were analyzed using the ICP-MS technique. Overall, six elements showed significance between the two groups, arsenic (As) was present at 0.68 μg/L in cases and absent in controls, while lead (Pb) exhibited elevated concentrations in the case group at 4.56 μg/L compared to 0.25 μg/L in controls, well-known for their toxicity. Barium (Ba) and manganese (Mn) levels were also higher in cases, associated with reported health effects on child well-being. Essential elements molybdenum (Mo) and selenium (Se) were higher in the controls. Furthermore, the association of these metals with the child growth standards as per WHO guidelines was calculated. Linear regression analysis revealed As negatively associated with WAZ and WHZ scores, while Mo was positively associated with WAZ, WHZ, and HAZ scores. These findings highlight serious health concerns in the region, where toxic elements pervade drinking water and food sources. Immediate actions are imperative to maintain the wellness of future generations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)