Is maternal body weight or composition associated with onset of lactogenesis II, human milk production or infant consumption of mother's own milk? A systematic review and meta-analysis.

Maternal adiposity impacts lactation performance, but the pathways are unclear. We conducted a systematic review to understand whether maternal adiposity (body mass index [BMI] or % fat mass) is associated with onset of lactogenesis II (copious milk; hours), human milk production (expressed volume/24hrs), and infant consumption of mother's own milk (volume/24hrs). We used random-effects standard meta-analyses to compare the relative risk (RR) of delayed lactogenesis II (>72 hours) between mothers classified as underweight (BMI <18.5kg/m2), healthy weight (BMI 18.5-24.9 kg/m2), and overweight/obese (BMI >25kg/m2) and random-effects meta-regressions to examine associations with hours to lactogenesis II and infant milk consumption. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. We included 122 articles. Mothers with underweight (RR: 0.61; 95% CI: 0.46, 0.83; I2= 46.27%; 8 articles/datapoints) or healthy weight status (RR: 0.72; 95% CI: 0.61, 0.84; I2= 64.41%; 15 articles/datapoints) were less likely to experience delayed lactogenesis II than mothers with overweight/obesity. We found no association between maternal BMI and time onset of lactogenesis II (ß= 1.45 hours; 95% CI: -3.19, 6.09; p= 0.52, I2= 0.00%; 8 articles, 15 datapoints). Due to limited data, we narratively reviewed articles examining BMI or % fat mass and milk production (n=6); half reported an inverse association, and half no association. We found no association between maternal BMI (ß= 5.84mL; 95% CI: -11.92, 23.60; p= 0.51, I2= 44.18 %; 58 articles, 75 datapoints) nor % fat mass (ß= 6.54mL; 95% CI: -3.60, 16.68; p= 0.20, I2= 21.40%; 30 articles, 32 datapoints) and infant milk consumption. Certainty of evidence for all outcomes was very low. In conclusion, mothers with overweight/obesity may be at risk of delayed lactogenesis II. Available data do not support an association with infant milk consumption but included studies do not adequately represent mothers with obesity. PROSPERO REGISTRATION #: 285344 STATEMENT OF SIGNIFICANCE: While results suggest mothers with overweight/obesity may be at risk of delayed lactogenesis II, it is important to note that available data do not adequately represent mothers at the higher end of the BMI and % fat mass spectrum (BMI >30 kg/m2, % fat mass >40%). Future research should explore the association between maternal body weight or composition and lactation outcomes including onset of lactogenesis II, human milk production and infant consumption of mother's own milk among mothers with greater variability in weight status. Understanding these relationships may help guide the creation of more specialized lactation care for mothers of all body sizes.

Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines.

Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin-adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring's metabolic homeostasis.

Associations between Bronchopulmonary Dysplasia, Insulin-like Growth Factor I and Nutrition.

Insulin-like growth factor I (IGF-I) has been suggested as an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD). In turn, nutrition has been associated with IGF-I levels and could be of importance in the pathogenesis of BPD. This study aimed to explore the association between nutrition, the IGF-I axis and the occurrence of BPD. Eighty-six preterm infants (44 male, mean gestational age: 29.0 weeks (standard deviation: 1.7 weeks)) were enrolled in an observational study. Serum IGF-I (µg/L) and insulin-like growth factor binding protein 3 (IGFBP-3; mg/L) were measured at birth and at 2, 4 and 6 weeks postnatal age. BPD was diagnosed at 36 weeks postmenstrual age. Twenty-nine infants were diagnosed with BPD. For every µg/L per week increase in IGF-I, the odds of BPD decreased (0.68, 95% CI 0.48-0.96, corrected for gestational age). The change in IGF-I in µg/L/week, gestational age in weeks and a week of predominant donor human milk feeding were associated with the occurrence of BPD in the multivariable analysis (respectively, OR 0.63 (0.43-0.92), OR 0.44 (0.26-0.76) and 7.6 (1.2-50.4)). IGFBP-3 was not associated with the occurrence of BPD in the multivariable analysis. In conclusion, a slow increase in IGF-I levels and a lower gestational age increase the odds of BPD. Donor human milk might increase the odds of BPD and should be further explored.

The Role of Maternal Secretor Status and Human Milk Oligosaccharides on Early Childhood Development: A Systematic Review and Meta-Analysis.

Background: Breast milk is the gold standard of infant nutrition, delivering nutrients and bioactive molecules as needed to support optimal infant growth and cognitive development. Increasing evidence links human milk oligosaccharides (HMOs) to these early childhood development milestones. Aims: To summarize and synthesize the evidence relating to HMOs and infant brain development, physical growth, and cognitive development. In addition, HMO concentrations in secretor and nonsecretor mothers were compared via a meta-analysis. Study Design: A systematic review and meta-analysis were carried out in accordance with the PRISMA statement. This review used three databases (PubMed, Scopus, and Web of Science) and was limited to English-language articles published between 2000 and June 30, 2023. Results: The initial searches yielded 245 articles, 27 of which were included in the systematic review and 12 in the meta-analysis. The meta-analysis revealed a substantial between-study heterogeneity, I2 = 97.3%. The pooled effect was 0.21 (95% CI: -0.41 to 0.83; p = 0.484), indicating that secretors had higher HMO concentrations, although this difference was not statistically significant. At one month of age, 2'FL, 3FL, and 3'SL play an important role in brain maturation and thus play a critical role in cognitive development. Secretors produce higher concentrations of 2'FL and 3'SL, explaining the benefits to infants of secretor mothers. Growth velocity was correlated to fucosylated and sialylated HMO concentrations, with lower concentrations linked to stunting. Conclusions: According to evidence from the systematically reviewed articles, HMOs are essential for a child's early development, but the extent to which they have an impact depends on maternal secretor status.

Potential biological functions and future perspectives of sialylated milk oligosaccharides.

Sialyllactoses (SLs) primarily include sialylated human milk oligosaccharides (HMOs) and bovine milk oligosaccharides (BMOs). First, the safety assessment of 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) revealed low toxicity in various animal models and human participants. SLs constitute a unique milk component, highlighting the essential nutrients and bioactive components crucial for infant development, along with numerous associated health benefits for various diseases. This review explores the safety, biosynthesis, and potential biological effects of SLs, with a specific focus on their influence across various physiological systems, including the gastrointestinal system, immune disorders, rare genetic disorders (such as GNE myopathy), cancers, neurological disorders, cardiovascular diseases, diverse cancers, and viral infections, thus indicating their therapeutic potential.

The acceptability of a donor human milk bank and donated human milk among mothers in Limpopo Province, South Africa.

Breastfeeding is a crucial public health approach that reduces infant morbidity and mortality by providing essential nutrients and antibodies, and breast milk is easily digested. Breastfeeding and donated milk serve as a preventative measure against necrotising enterocolitis. Additionally, they protect against viruses and nosocomial sepsis. When a birthing parent's own milk is unavailable, alternative enteral nutrition for preterm or low-birth-weight infants is either donor human milk (DHM) or artificial formula. This study aimed to understand mothers' acceptance of the donor human milk bank (DHMB) and DHM. A qualitative phenomenological study was conducted in Limpopo Province, South Africa. The study used purposive sampling to select 23 mothers in postnatal and neonatal wards. Data collection was via in-depth interviews using a semistructured interview guide. Manual data analysis using an interpretative phenomenological analysis (IPA) framework was used to coding. Concepts were grouped to generate themes. Three themes and nine subthemes were generated: (1) DHMBs (2) cultural perspective of DHMB, and (3) health considerations of DHM. Participants were unaware of the DHMB. Hesitancy in accepting DHM due to fear of contracting HIV was observed. Cultural beliefs are an influencing factor for use, while donation was driven by altruistic reasons, preventing waste, helping others and having previously benefited from DHM. The study found that mothers are willing to donate human milk. Willingness to donate can be increased by raising awareness about DHMB and addressing culture and safety concerns at antenatal clinics.

Knowledge, Attitudes, and Perceptions of Medical and Paramedical Students Toward Human Milk Banks and Breast Milk Donation.

Background and objectives Human milk benefits for both mothers and babies are widely acknowledged. Human milk banks (HMBs) are essential in providing newborns who would not otherwise have access to pasteurized and stored human milk. The objective of this research was to investigate the understanding, opinions, and outlooks of medical and paramedical students regarding breast milk donation and the concept of an HMB. Material and methods A total of 398 professional female students specializing in physiotherapy, nursing, and medicine were given an online self-administered questionnaire as part of a descriptive cross-sectional study. Data on the characteristics, HMB knowledge, awareness levels, and attitudes toward HMB and breast milk donation were to be gathered through the questionnaire. Every student's answer to the survey was kept private and confidential. Result According to the survey, 188 students (47.24%) belong to the medical college, 126 students (31.66%) belong to the physiotherapy college, and the remaining 84 students (21.11%) are from the nursing college. A total of 294 students (74.12%) had heard about human milk banking before and received information from health professionals (195 students, 48.99%), the news (67 students, 16.83%), and family and friends (61 students, 15.33%). However, only 224 students (56.28%) are willing to feed their babies with HMB milk in the future. On the other hand, 216 students (54.27%) are ready to donate breast milk to HMB. The majority of students have a favorable opinion of breast milk donation. A staggering 394 students (98.99%) think that donating human milk can save babies. Furthermore, 379 students (95.23%) think that all the nutrients needed for a baby's healthy development are found in human milk. Merely 350 students (87.93%) think that breastfeeding does not result in malnourishment for either the mother or the baby. When there is an excess of milk, the majority of students (378 or 94.97%) think that there is nothing wrong with donating it. Moreover, 312 (80.41%) students are happy to donate milk in the future. A total of 373 students (93.71%) are overjoyed that a sick baby will survive because of their donated milk. Only 100 students (25.12%) will give milk, though, and only to the infants of their friends and relatives, never to complete strangers. Conclusion A dearth of knowledge pertaining to human milk banking is rampant among medical and paramedical female students, yet the gravity of the circumstances remains concealed. Consequently, it is imperative to extensively educate all Indian communities about the concept of human milk banking to gain widespread acceptance. This research sheds light on the issue and promotes scientific knowledge of HMB, as many students are unaware of it.

Donation barriers, enablers, patterns and predictors of milk bank donors in the United States and United Kingdom.

Pasteurised donor human milk is recommended for very low birthweight infants who do not have access to their mother's milk. Although the use of donor milk continues to increase, little is known about the donation experiences of milk bank donors. We aimed to describe and compare enablers, barriers and patterns of human milk donation and identify factors predicting donation volume in a convenience sample of approved milk bank donors in the United Kingdom and the United States. A cross-sectional online survey was conducted from August 2022 to December 2022. Approved milk bank donors (n = 556) from three milk banks in the United States (n = 369, Mothers' Milk Bank of Florida, Mother's Milk Bank of North Texas and Northwest Mothers Milk Bank) and one milk bank in the United Kingdom (n = 187, Hearts Milk Bank) completed the survey. A substantial portion of donors in both settings reported participating in other forms of milk exchange (51% of U.S. donors vs. 39% of UK donors, p = 0.009). Top donation barriers reported in both settings were completing the serological screening and having enough space to store collected milk. Most donors started donating when their infant was 3 months old or older and reported donating mature milk. The most common source of information related to milk banking in each setting was the internet (United Kingdom-70% vs. United States - 63%, p = 0.112). Variables that predicted lifetime donation volume differed between the United States and the United Kingdom, highlighting the importance of setting-specific milk banking research.

Essential and non-essential element concentrations in human milk samples and the assessment of infants' exposure.

As the data concerning element concentrations in human milk (HM) samples and their intake by infants are lacking in Poland, the present study aimed to explore this issue. The material consisted of HM samples obtained from 30 exclusively breastfeeding mothers during 4-6 weeks postpartum. Additionally, to identify the factors that may potentially affect HM composition, information regarding maternal data (anthropometry, body composition, and diet) was also collected. Maternal diet was assessed with two methods-a food frequency questionnaire and 3-day dietary records. In total, 18 essential and non-essential elements were determined. For the elements analysis, we used inductively coupled plasma quadrupole mass spectrometry. Most of the elements (n = 11, 61%) were detected in all HM samples. In all HM samples tin concentration was higher (5.67 ± 2.39 µg/L) than the usual range reported by the World Health Organization (~ 1.0 µg/L). HM cadmium content was positively associated with maternal salty snacks intake (r = 0.502, p = 0.005), arsenic with whole-grain products intake (r = 0.37, p = 0.043), and mercury concentration with fruits and seeds/nuts consumption (r = 0.424, p = 0.042 and r = 0.378, p = 0.039, respectively). Higher HM lead concentration was predicted by maternal age (95% CI [0.94-0.97]), intake of fish (95% CI [1.01-1.03]), and vegetables (95% CI [1.02-1.06]). The highest infants' intake was observed for copper (35.24 ± 12.48) and the lowest for arsenic (0.076 ± 0.102). Infants' exposure to lead was associated with maternal frequency consumption of canned fish (p = 0.0045). There is a need to perform further research on this topic to maximize the benefits of breastfeeding by minimizing maternal and infant exposure to potentially toxic elements.

O-linked glycosylations in human milk casein and major whey proteins during lactation.

As glycosylations are difficult to analyze, their roles and effects are poorly understood. Glycosylations in human milk (HM) differ across lactation. Glycosylations can be involved in antimicrobial activities and may serve as food for beneficial microorganisms. This study aimed to identify and analyze O-linked glycans in HM by high-throughput mass spectrometry. 184 longitudinal HM samples from 66 donors from day 3 and months 1, 2, and 3 postpartum were subjected to a post-translational modification specific enrichment-based strategy using TiO2 and ZrO2 beads for O-linked glycopeptide enrichment. ß-CN was found to be a major O-linked glycoprotein, additionally, αS1-CN, κ-CN, lactotransferrin, and albumin also contained O-linked glycans. As glycosyltransferases and glycosidases are involved in assembling the glycans including O-linked glycosylations, these were further investigated. Some glycosyltransferases and glycosidases were found to be significantly decreasing through lactation, including two O-linked glycan initiator enzymes (GLNT1 and GLNT2). Despite their decrease, the overall level of O-linked glycans remained stable in HM over lactation. Three different motifs for O-linked glycosylation were enriched in HM proteins: Gly-Xxx-Xxx-Gly-Ser/Thr, Arg-Ser/Thr and LysSer/Thr. Further O-linked glycan motifs on ß-CN were observed to differ between intact proteins and endogenous peptides in HM.

Neonatal enteroids absorb extracellular vesicles from human milk-fed infant digestive fluid.

Human milk contains extracellular vesicles (HMEVs). Pre-clinical models suggest that HMEVs may enhance intestinal function and limit inflammation; however, it is unknown if HMEVs or their cargo survive neonatal human digestion. This limits the ability to leverage HMEV cargo as additives to infant nutrition or as therapeutics. This study aimed to develop an EV isolation pipeline from small volumes of human milk and neonatal intestinal contents after milk feeding (digesta) to address the hypothesis that HMEVs survive in vivo neonatal digestion to be taken up intestinal epithelial cells (IECs). Digesta was collected from nasoduodenal sampling tubes or ostomies. EVs were isolated from raw and pasteurized human milk and digesta by density-gradient ultracentrifugation following two-step skimming, acid precipitation of caseins, and multi-step filtration. EVs were validated by electron microscopy, western blotting, nanoparticle tracking analysis, resistive pulse sensing, and super-resolution microscopy. EV uptake was tested in human neonatal enteroids. HMEVs and digesta EVs (dEVs) show typical EV morphology and are enriched in CD81 and CD9, but depleted of ß-casein and lactalbumin. HMEV and some dEV fractions contain mammary gland-derived protein BTN1A1. Neonatal human enteroids rapidly take up dEVs in part via clathrin-mediated endocytosis. Our data suggest that EVs can be isolated from digestive fluid and that these dEVs can be absorbed by IECs.

Effects of oropharyngeal administration of own mother's milk on oral microbial colonization in very low birth weight infants fed by gastric tube: A randomized controlled trial.

AIMS: The aim of the present study was to explore the effect of oropharyngeal mother's milk administration on oral microbial colonization in infants fed by gastric tube at different time points. METHODS: Infants (n = 116) with birth weight <1500 g were randomly allocated into two groups which both received breast milk for enteral nutrition. The control group (n = 51) accepted oropharyngeal normal saline administration. The experimental group (n = 53) accepted oropharyngeal mother's milk administration before fed by gastric tube once every 3 h over 21 days after birth. We analyzed the oral microbiota at initiation and 7 and 14 and 21 days later using 16S DNA amplicon sequencing. RESULTS: There were no difference in oral microbial diversity between the two groups at any time point, but diversity decreased significantly over time in both groups. On the first day of life, the oral microbiota of the infant in the experimental and control groups consisted mainly of Firmicutes (7.75%, 6.18%) and Proteobacteria (68.65%, 68.69%), respectively. As time increases to 21 days after birth, Firmicutes (77.67%, 77.66%) had replaced Proteobacteria (68.65%, 68.69%) as the predominant phylum. DISCUSSION: From birth to 21 days after birth, oropharyngeal mother's milk administration did not change the diversity and structural composition of the oral microbiota. The oral microbial diversity of infants declined significantly over time. Firmicutes had replaced Proteobacteria as the predominant phylum.

Breastfeeding patterns in one-year-old children was not affected by a breastfeeding support intervention.

BACKGROUND: Breastfeeding patterns in 12-month-old children play a central role in the mother-infant dyad, but studies describing the patterns are scarce. AIM: To investigate breastfeeding patterns in 12-month-old infants before and after a breastfeeding support programme. STUDY DESIGN: A baseline/intervention design as part of a larger implementation project aiming to revive the Ten Steps to Successful Breastfeeding programme. SUBJECTS: During a 24-h period, 28 mothers from a baseline group and 24 mothers from an intervention group recorded all breastfeeding sessions on a pen and paper form. RESULTS: The median (range) frequency of breastfeeding sessions was 6 (1-22) in the baseline group and 7 (1-20) times per 24 h in the intervention group. No significant difference was observed in frequencies between the two groups. The majority of children (57 % in the baseline group and 62 % in the intervention group) exhibited a pattern classified as partial breastfeeding, engaging in breastfeeding 6 or more times per 24 h throughout a substantial part of the day. A second pattern was classified as token breastfeeding, with few breastfeeding sessions, suggesting that breastfeeding occurred primarily for comfort. CONCLUSION: This study illuminates the breastfeeding behaviours of 12-month-old children and can serve to normalise frequent breastfeeding patterns, potentially aiding mothers who wish to continue breastfeeding beyond infancy. The findings indicate no difference between the groups, suggesting that the implemented intervention did not influence maternal breastfeeding practices at one year of age. This underscores the potential necessity for prolonged support for parents throughout the breastfeeding period. ISRCTN registry: doi.org/10.1186/ISRCTN91972905.

Effects of human milk odor stimulation on feeding in premature infants: a systematic review and meta-analysis.

Previous studies suggested odor stimulation may influence feeding of premature neonates. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of human milk odor stimulation on feeding of premature infants. All randomized controlled trials related to human milk odor stimulation on feeding in premature infants published in PubMed, Cochrane, Library, Medline, Embase, Web of science databases and Chinese biomedical literature databases, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP) and Wanfang Chinese databases were searched, and The Cochrane Handbook 5.1.0 was used to evaluate the quality and authenticity of the literature. Relevant information of the included studies was extracted and summarized, and the evaluation indexes were analyzed using ReviewManager5.3. The retrieval time was from the establishment of the database to July 28, 2022.12 articles were assessed for eligibility, and six randomized controlled studies were eventually included in the meta-analysis (PRISMA). A total of 6 randomized controlled studies with 763 patients were finally included in the study, and the quality evaluation of literatures were all grade B. Human milk odor stimulation reduced the transition time to oral feeding in premature infants [SMD = - 0.48, 95% CI (- 0.69, - 0.27), Z = 4.54, P < 0.00001] and shortened the duration of parenteral nutrition [MD = - 1.01, 95% CI (- 1.70, - 0.32), Z = 2.88, P = 0.004]. However, it did not change the length of hospitalization for premature infants [MD = - 0.03, 95% CI (- 0.41, 0.35), Z = 0.17, P = 0.86]. The implementation of human milk odor stimulation can reduce the transition time to oral feeding and the duration of parenteral nutrition in premature infants, but further studies are needed to determine whether it can reduce the length of hospital stay in premature infants. More high-quality, large-sample studies are needed to investigate the effect of human milk odor stimulation on the feeding process and other outcomes in premature infants.

Handling of human milk to prevent acquired cytomegalovirus infection in Japanese neonatal intensive care units: The first nationwide survey.

BACKGROUND: Human milk (HM) has been proven to provide immunological and nutritional advantages to neonates; however, acquired cytomegalovirus (CMV) infection can be associated with raw HM. In Japan, there are no standardized guidelines concerning HM handling. This cross-sectional survey was performed to reveal specific trends in HM handling in neonatal intensive care units (NICUs) in Japan. METHODS: A questionnaire was sent to 255 NICUs participating in the Japanese Neonatologist Association in May 2020. It involved HM handling practices, such as maternal screening, pasteurization, storage, and the workforce. RESULTS: Of 255 NICUs, 174 (67.8%) responded to the survey. Maternal CMV screening was carried out in 37 units (22.2%), and CMV inactivation in HM was performed in 44 units (26.5%). For CMV inactivation, a freeze-thawing method was employed in about 90% of units. In 70% of units providing CMV inactivation, CMV inactivation was conducted regardless of bodyweight and corrected gestational age of infants until the infants' discharge. Acquired CMV infection in preterm neonates was observed in 43 units (25.7%) in the survey period. CONCLUSION: A wide range of HM handling practices are used in Japanese NICUs. A national guideline for handling HM in NICUs should be created to promote the infection control of CMV.

Evaluation of Prebiotic Glycan Composition in Human Milk and Infant Formula: Profile of Galacto-Oligosaccharides and Absolute Quantification of Major Milk Oligosaccharides by UPLC-Cyclic IM-MS and UPLC-MS/MS.

Prebiotic oligosaccharides have attracted immense interest in the infant formula (IF) industry due to their unique health benefits for infants. There is a need for the reasonable supplementation of prebiotics in premium IF products. Herein, we characterized the profile of galacto-oligosaccharides (GOS) in human milk (HM) and IF using ultrahigh-performance liquid chromatography-cyclic ion mobility-mass spectrometry (UPLC-cIM-MS) technique. Additionally, we further performed a targeted quantitative analysis of five essential HM oligosaccharides (HMOs) in HM (n = 196), IF (n = 50), and raw milk of IF (n = 10) by the high-sensitivity UPLC-MS/MS method. HM exhibited a more abundant and variable HMO composition (1183.19 to 2892.91 mg/L) than IF (32.91 to 56.31 mg/L), whereas IF contained extra GOS species and non-negligible endogenous 3'-sialyllactose. This also facilitated the discovery of secretor features within the Chinese population. Our study illustrated the real disparity in the prebiotic glycome between HM and IF and provided crucial reference for formula improvement.

Recent Progress in Human Milk Oligosaccharides and Its Antiviral Efficacy.

Gastrointestinal (GI)-associated viruses, including rotavirus (RV), norovirus (NV), and enterovirus, usually invade host cells, transmit, and mutate their genetic information, resulting in influenza-like symptoms, acute gastroenteritis, encephalitis, or even death. The unique structures of human milk oligosaccharides (HMOs) enable them to shape the gut microbial diversity and endogenous immune system of human infants. Growing evidence suggests that HMOs can enhance host resistance to GI-associated viruses but without a systematic summary to review the mechanism. The present review examines the lactose- and neutral-core HMOs and their antiviral effects in the host. The potential negative impacts of enterovirus 71 (EV-A71) and other GI viruses on children are extensive and include neurological sequelae, neurodevelopmental retardation, and cognitive decline. However, the differences in the binding affinity of HMOs for GI viruses are vast. Hence, elucidating the mechanisms and positive effects of HMOs against different viruses may facilitate the development of novel HMO derived oligosaccharides.

De Novo Biosynthesis of Difucosyllactose by Artificial Pathway Construction and α1,3/4-Fucosyltransferase Rational Design in Escherichia coli.

Difucosyllactose (DFL) is a significant and plentiful oligosaccharide found in human breast milk. In this study, an artificial metabolic pathway of DFL was designed, focusing on the de novo biosynthesis of GDP-fucose from only glycerol. This was achieved by engineering Escherichia coli to endogenously overexpress genes manB, manC, gmd, and wcaG and heterologously overexpress a pair of fucosyltransferases to produce DFL from lactose. The introduction of α-1,2-fucosyltransferase from Helicobacter pylori (FucT2) along with α-1,3/4-fucosyltransferase (HP3/4FT) addressed rate-limiting challenges in enzymatic catalysis and allowed for highly efficient conversion of lactose into DFL. Based on these results, molecular modification of HP3/4FT was performed based on computer-assisted screening and structure-based rational design. The best-performing mutant, MH5, containing a combination of five mutated sites (F49K/Y131D/Y197N/E338D/R369A) of HP3/4FT was obtained. The best strain BLC09-58 harboring MH5 yielded 45.81 g/L of extracellular DFL in 5-L fed-batch cultures, which was the highest titer reported to date.

Fucosylated human milk oligosaccharide-utilizing bifidobacteria regulate the gut organic acid profile of infants.

Bifidobacteria are the predominant bacteria in the infant gut and have beneficial effects on host physiology. Infant cohort studies have demonstrated that a higher abundance of bifidobacteria in the gut is associated with a reduced risk of disease. Recently, bifidobacteria-derived metabolites, such as organic acid, have been suggested to play crucial roles in host physiology. This review focuses on an investigation of longitudinal changes in the gut microbiota and organic acid concentrations over 2 years of life in 12 Japanese infants and aims to identify bifidobacteria that contribute to the production of organic acid in healthy infants. Acetate, lactate, and formate, which are rarely observed in adults, are characteristically observed during breast-fed infancy. Bifidobacterium longum subspecies infantis and the symbiosis of Bifidobacterium bifidum and Bifidobacterium breve efficiently produce these organic acids through metabolization of human milk oligosaccharide (HMO) with different strategies. These findings confirmed that HMO-utilizing bifidobacteria play an important role in regulating the gut organic acid profiles of infants.

Associations of Early Gut Microbiome and Metabolome with Growth and Body Composition of Preterm Infants Within the First 6 Months.

Objectives: This study aimed to explore the associations of growth and body composition with gut microbiome and metabolome in preterm infants. Materials and Methods: A prospective cohort study including 73 human milk-fed very preterm infants was conducted. During hospitalization, fecal samples were collected to detect microbes and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Growth and body composition indices were measured at term equivalent age (TEA) and 6 months of corrected age (CA). Associations of the fecal microbiome and metabolome profiles with growth and body composition indices, as well as their changes, were analyzed. Results: A higher abundance of Streptococcus was associated with a lower fat-free mass (FFM) z-score at 6 months of CA (p = 0.002) and a smaller increase in FFM z-score from TEA to 6 months of CA (p = 0.018). Higher levels of 3'-sialyllactose and 6'-sialyllactose (6'-SL) in feces were correlated with a lower z-score of percentage body fat (PBF) (p = 0.018 and 0.020, respectively) and a lower z-score of fat mass (p = 0.044 and 0.043, respectively) at 6 months of CA. A higher level of 6'-SL in feces was correlated with a greater increase in FFM z-score from TEA to 6 months of CA (p = 0.021). Conclusions: This study sheds light on the role of specific microbial-host interactions in metabolic changes in preterm infants, indicating the potential role of sialylated human milk oligosaccharides in optimizing body composition.