Human milk sphingomyelin: Function, metabolism, composition and mimicking.

Human milk, which contains various nutrients, is the "gold standard" for infant nutrition. Healthy human milk meets all the nutritional needs of early infant development. Polar lipids mainly exist in the milk fat globule membrane, accounting for approximately 1-2% of human milk lipids; sphingomyelin (SM) accounts for approximately 21-24% of polar lipids. SM plays an important role in promoting the development of the brain and nervous system, regulating intestinal flora, and improving skin barriers. Though SM could be synthesized de novo, SM nutrition from dietary is also important for infants. The content and composition of SM in human milk has been reported, however, the molecular mechanisms of nutritional functions of SM for infants required further research. This review summarizes the functional mechanisms, metabolic pathways, and compositional, influencing factors, and mimicking of SM in human milk, and highlights the challenges of improving maternal and infant early/long-term nutrition.

Comparative evaluation of enriched formula milk powder with OPO and MFGM vs. breastfeeding and regular formula milk powder in full-term infants: a comprehensive study on gut microbiota, neurodevelopment, and growth.

This study investigated the non-inferiority of feeding term healthy infants with enriched formula milk powder containing 1,3-dioleoyl-2-palmitoylglycerol (OPO) and milk fat globular membrane (MFGM), compared to breast milk, in terms of the formation of gut microbiota, neurodevelopment and growth. Infants were divided into three groups: breast milk group (BMG, N = 50), fortified formula group (FFG, N = 17), and regular formula group (RFG, N = 12), based on the feeding pattern. Growth and development information was collected from the infants at one month, four months, and six months after the intervention. Fecal samples were collected from infants and analyzed for gut microbiota using 16S ribosomal DNA identification. The study found that at the three time points, the predominant bacterial phyla in FFG and BMG were Proteobacteria, Firmicutes, and Bacteroidetes, which differed from RFG. The abundance of Bifidobacterium in the RFG was lower than the FFG (one month, p = 0.019) and BMG (four months, p = 0.007). The abundance of Methanoprebacteria and so on (genus level) are positively correlated with bone mineral density (BMD) of term infants, and have the potential to be biomarkers for predicting BMD. The abundance of beta-galactosidase, a protein that regulates lactose metabolism and sphingoid metabolism, was higher in FFG (six months, p = 0.0033) and BMG (one month, p = 0.0089; four months, p = 0.0005; six months, p = 0.0005) than in the RFG group, which may be related to the superior bone mineral density and neurodevelopment of infants in the FFG and BMG groups than in the RFG group. Our findings suggest that formula milk powder supplemented with OPO and MFGM is a viable alternative to breastfeeding, providing a practical alternative for infants who cannot be breastfed for various reasons.

Effects of lipids from multiple sources on glyceride composition, concentration, and structure of infant formulas benchmarked to human milk.

The important parameters affecting the nutritional properties of lipids were analyzed and compared between human milk (HM), infant formulas (IFs), mammalian milk, and substitute fat, including molecular species, fatty acid composition, glyceride content, and important structural triacylglycerols (TAGs). The molecular species of triacylglycerols with functional fatty acids were significantly different between HM and IFs, and their contents in HM were significantly higher than those in IFs. Accordingly, the evaluation scores of fatty acid composition and glyceride content in IFs were less than 50 compared to HM. Although the introduction of vegetable oils effectively improved the unsaturation of IF lipid, the excessive addition of TAGs rich in oleic and linoleic acid resulted in an imbalance of TAG composition and structure. Only 36.84 % of IFs were supplemented with structured lipids, but those still lacked sn-2 palmitate TAGs. The adoption of multiple lipids and novel processing technologies is required for novel IFs to match the composition, content, positional structure and spherical membrane structure of HM as closely as possible.

Tuning active sites for highly efficient bifunctional oxygen electrocatalysts of rechargeable zinc-air battery.

High activity, excellent durability, and low-cost oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) bifunctional catalysts are highly required for rechargeable zinc (Zn)-air batteries. Herein, we designed an electrocatalyst by integrating the ORR active species of ferroferric oxide (Fe3O4) and the OER active species of cobaltous oxide (CoO) into the carbon nanoflower. By well regulating and controlling the synthesis parameters, Fe3O4 and CoO nanoparticles were uniformly inserted into the porous carbon nanoflower. This electrocatalyst can reduce the potential gap between the ORR and OER to 0.79 V. The Zn-air battery assembled with it exhibited an open-circuit voltage of 1.457 V, a stable discharge of 98 h, a high specific capacity of 740 mA h g-1, a large power density of 137 mW cm-2, as well as good charge/discharge cycling performance, exceeding the performance of platinum/carbon (Pt/C). This work provides references for exploring highly efficient non-noble metal oxygen electrocatalysts by tuning ORR/OER active sites.

Diversity and temporal dynamics of breast milk microbiome and its influencing factors in Chinese women during the first 6 months postpartum.

Human breast milk (HBM) plays an important role in providing nutrients, beneficial microorganisms and bioactive components for infants, helping maturation of their immune system and gastrointestinal development. Here, we present a study aiming to investigate the diversity and temporal dynamics of the milk microbiome across the first 6 month postpartum in Chinese healthy breastfeeding women, and to investigate to what extent other variables (e.g., sampling location, infant sex, and mode of delivery) might also be related to variations in the human milk microbiome, and the association with maternal diet and nutrients. Fifty-three healthy pregnant women from four cities were recruited from a China Maternal and Infant Health Cohort Study and breast milk samples were collected and analyzed using 16S rRNA metagenomic sequencing. We illustrated the diversity and temporal dynamics during lactation (Adonis p-value = 3e-04). Firmicutes and Proteobacteria were the most abundant phyla, and Streptococcus, Staphylococcus, Serratia, and Corynebacterium were the core genera. Partitioning around medoids clustering identified two major internal clusters of breast milk microbiota. Cluster 1 was dominated by Acinetobacter and Pseudomonas, while Cluster 2 was dominated by Streptococcus and Staphylococcus. Among other environmental variables, sampling location showed significant influence on breast milk microbiome (Adonis p-value = 4e-04), while infant sex (Adonis p-value = 0.33) and mode of delivery (Adonis p-value = 0.19) were less related to variations in the human milk microbiome. Maternal diet such as tuber was significantly correlated with the relative abundance of Neisseria (rho = 0.34, adjusted p-value = 0.01) and Cutibacterium (rho = -0.35, adjusted p-value = 0.01), and nutrients such as carbohydrates were significantly correlated with the relative abundance of Aquabacterium (rho = -0.39, adjusted p-value = 0.0027), and vitamin B12 was significantly correlated with the relative abundance of Coprococcus (rho = 0.40, adjusted p-value = 0.0018), etc. These results illustrated the dynamic changes of composition and diversity during the lactation phases of the Chinese breast milk microbiome and addressed the importance of geographic location on milk microbiota, and associations with maternal diet consumption, which have potential benefits on the establishment and future health of breastfeeding infants.

MYBIOTA: A birth cohort on maternal and infant microbiota and its impact on infant health in Malaysia.

Background: The microbiota plays a key role in early immunity maturation that affects infant health and is associated with the development of non-communicable diseases and allergies in later life. Objective: The MYBIOTA is a prospective mother-infant cohort study in Malaysia aiming to determine the association between gut microbiota with infant health (temperament, gastrointestinal disorders, eczema, asthma, and developmental delays) in Selangor, Malaysia. Methods: Pregnant mothers will be enrolled in their first trimester of pregnancy, and follow-ups will be done for infants during their first year of life. Maternal-infant biological samples (blood, feces, saliva, urine, and breast milk), anthropometric, dietary, and clinical information will be collected at different time points from early pregnancy to 12 months postpartum. Discussion: This study could provide a better understanding of the colonization and development of the gut microbiome during early life and its impact on infant health. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04919265.

Bovine milk with variant ß-casein types on immunological mediated intestinal changes and gut health of mice.

Dietary proteins provide bioactive peptides, which are important for host gastrointestinal functions. We hypothesized that A2-type ß-casein could provide gastrointestinal benefits and improve the immune and gut health. This study was conducted to investigate those effects and mechanisms. Thirty BALB-c mice (3-4 weeks old) were fed with either a control diet (control), a diet supplemented with bovine milk containing A1 and A2 type ß-casein (A1A2, contains 63.62% A2 ß-casein of total ß-casein) or a diet containing A2 type ß-casein (A2A2, contains 95.96% A2 ß-casein of total ß-casein) (10 ml/kg body weight) for 4 weeks. Immunoglobulin and inflammation factors were measured in serum, and histological variations were measured in duodenal and ileum, and stool 16S rRNA and short-chain fatty acids (SCFAs) contents were measured in fecal samples. Results showed that consumption of A2-type ß-casein milk could improve proximal small intestine villus and crypt morphology (p < 0.05), increase IgG and IgE responses, and modulate the composition and diversity of gut microbiota by increase the relative abundance of phylum Proteobacteria, class Clostridia, family Ruminococcaceae and species Lactobacillus animalis (p < 0.05). There were also significant associations between gut microbes, immune response, and SCFAs, especially isobutyric acid (p < 0.05), which may potentially regulated gastrointestinal benefits. Moreover, intake of A2-type ß-casein milk had no impact on inflammation. These findings explained potential benefits of consumption of A2-type ß-casein milk on host immune system and gut health outcomes, and provide insights to the future application of nutritional modulation.

Specially designed yogurt supplemented with combination of pro- and prebiotics relieved constipation in mice and humans.

OBJECTIVE: Functional constipation is a gastrointestinal disorder that affects millions of people and is correlated with gut microbiome dysbiosis. The currently available treatments are ineffective; therefore, novel treatment schemes targeting the gut microbiome are desired. The aim of this study was to assess the effects of yogurt supplemented with seven probiotic strains and six types of dietary fibers on functional constipation. METHODS: In the mouse study, mice with induced constipation were administered the yogurt once a day for 1 wk, with fecal parameters and intestinal transit rate measured. In the clinical study, participants with constipation (N = 86) were given the yogurt once daily (200 g) for 4 wk. Fecal and blood samples along with Patient Assessment of Constipation-symptoms and Patient Assessment of Constipation-Quality of Life Scale questionnaires were collected to evaluate the safety and efficacy of the yogurt. Shotgun metagenomic sequencing was performed to analyze fecal samples of both mice and humans. RESULTS: We found that constipated mice had different gut microbiomes compared with those in healthy controls; yogurt treatment significantly relieved constipation-related symptoms and resulted in shifts in the microbiome. Yogurt also relieved symptoms of antibiotic-induced constipation in mice and restored the gut microbiome to a certain extent. In the clinical trial with 86 patients, yogurt administration significantly improved constipation symptoms and showed no serious adverse effects (was generally considered safe). However, subsequent metagenomic profiling of the gut microbiome did not reveal significant changes in the microbial composition, in contrast to the results in mice. We hypothesize that the differences in dosage between mice and humans may attribute to such discrepancies, and microbiome changes may not be necessary for improvements of constipation symptoms in humans. CONCLUSION: Results from this study showed that yogurt can potentially be used for the treatment of constipation.

Study on the characteristics of glycerides and phospholipids in human milk from Tibet.

The unique geographical characteristics and food culture of Tibet can affect the nutrition of human milk lipids. But little has been done in the comparison of the lipids between Tibet and other areas. This study gives in-depth analysis of the species, concentration and composition of lipid subclasses at the molecular level of the Tibetan human milk. There were averagely 132 ± 30 species of lipids, among which triglycerides (TAGs), phosphatidylethanolamine (PE) and sphingomyelin (SM) accounted for 79.78% of the total species number in the Tibetan human milk samples. The contents of TAG, SM, phosphatidylcholine (PC), and PE in the Tibetan human milk were 85.84%, 17.79%, 25.94% and 55.81% of those in the comparative human milk of China, respectively. The contents of TAGs and diglycerides (DAGs) with PUFAs in Tibetan human milk were significantly lower than those in the comparative group. However, the content and percentage of TAGs and DAGs with odd-chain saturated fatty acids were both higher in the Tibetan human milk than those in the comparative human milk. In total, 18 molecular species of lipids were downregulated and 5 ones were upregulated in the Tibetan human milk compared with those in the comparative human milk of China. The profile of lipids in the Tibetan human milk at the molecular level provided the scientific basis for maternal diet and supplemented the Chinese human milk lipids database.

Three urban areas of China: a cohort study of maternal-infant factors and HM protein components.

This work studies the concentrations of proteins in human milk (HM) at different lactation periods and explores the influence of maternal-infant factors on the dynamics of HM proteins in a Chinese cohort. The cohort contained 153 mother-infant pairs, and 12 main proteins of 376 HM samples were analyzed. The result showed that physiological factors (age and pre-pregnancy BMI), demographic factors (education and occupation), endogenous factors (cesarean section), and exogenous factors (lactation period and area) could explain the dynamics of HM proteins, including the total protein, true protein, whey protein, ß-casein, lactoferrin, IgA, and IgM (R2 > 0.3). Factor analysis explained the dynamic changes in the IgM content by the highest degree of 49.5%. This study aimed to find the mother-infant factors that affected the dynamic changes in HM proteins, in order to optimize HM proteins and improve the long- and short-term health of infants (registration number: NCT02658500).

Distribution and Influencing Factors of the Sialic Acid Content in the Breast Milk of Preterm Mothers at Different Stages.

Background and Aims: This study aimed to detect breast milk sialic acid (SA) content and the changing pattern, to understand the various stages of breastfeeding SA secretion, and the influence factors of the human milk SA content. Methods: We recruited mothers and their infants as our subjects. At days 7, 14, 30, 120, and 365 after delivery, the contents of SA in breast milk were collected and detected through Fluorescence Detector-High Performance Liquid Chromatography. The participants completed the baseline questionnaire at ≤day 7 and were followed up at days 30, 120, and 365. Results: A total of 95 mothers with 122 infants were included in the analysis, including 22 mothers with 22 term infants, 25 mothers with 35 late preterm infants, 31 mothers with 39 very preterm infants, and 17 mothers with 26 extremely preterm infants. Similar to previous findings, the results of the study showed that, compared with breast milk of term mothers at the same period, breast milk of preterm mothers contained more SA at each time node, and the content of SA in breast milk increased with decreasing gestational weeks. Moreover, maternal age, pre-pregnancy BMI, and delivery mode had significant effects on total SA in breast milk, especially for the preterm infant breast milk. Significant negative associations occurred between SA contents and infant growth status, especially in preterm infants. Conclusions: We have confirmed the previous observations showing that with the prolongation of lactation time, the content of SA in breast milk gradually decreased, and the content of SA in the breast milk of preterm mothers was higher than that of term mothers. In addition, SA content was associated with maternal age, pre-pregnancy BMI, and delivery mode.

Quantification of phospholipids and glycerides in human milk using ultra-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry.

Human milk lipids, which are an important source of energy and affect growth and development of infants, require a comprehensive method for its qualitative and quantitative analysis. This work describes a method for the analysis of phospholipids, glycerides, free fatty acids and gangliosides in human milk by ultra-performance liquid chromatography using a C18 column with quadrupole-time-of-flight mass spectrometry (Q-TOF-MS). The lipids were extracted by liquid-liquid extraction and phospholipids were separated by solid phase extraction (SPE). The chromatographic columns with two different specifications (4.6 mm × 150 mm, and 3 mm × 50 mm) were used to detect phospholipids and glycerides in human milk, respectively. The sphingolipids and glycerides were analyzed in positive ion mode, and the glycerophospholipids and free fatty acids were analyzed in negative ion mode. Both internal and external standards were used for absolute quantification in this experiment. 483 species of lipids, including phospholipids, glycerides, free fatty acids and gangliosides, in human milk were analyzed using UPLC-Q-TOF-MS with high sensitivity and good linearity, with coefficient of correlation above 0.99, the relative standard deviation of accuracy and precision less than 10%. The results in a large number of human milk samples showed that this method was suitable for qualitative and quantitative analysis of lipids in human milk, even for other mammalian milk and infant formulae.

MFGM components promote gut Bifidobacterium growth in infant and in vitro.

PURPOSE: Infant gut microbiota which plays an important role in long-term health is mainly shaped by early life nutrition. However, the effect of nutrients on infants gut microbiota is less researched. Here, we present a study aiming to investigate in vitro a modified formula that is supplemented with milk fat globule membrane (MFGM) that were missing in common formulas when compared with human milk and to assess the impact of feeding scheme on microbiota and metabolism. METHODS: A total of 44 infants including 16 from breast milk feeding, 13 from common formula feeding and 15 from modified formula feeding were analyzed, and A cross-sectional sampling of fecal and urine was done at 1 month-of-age. Stool microbiota composition was characterized using high-throughput DNA sequencing, and urinary metabolome was profiled by nuclear magnetic resonance (NMR). In vitro growth experiment of Bifidobacterium with key components from MFGM was performed and analyzed by both DNA and RNA. RESULTS: Stool samples from the infants who were breastfed had a higher relative abundance of Bifidobacterium and a lower relative abundance of Escherichia than the formula-fed infants. The stool microbiome shifts were associated with urine metabolites changes. Three substances including lactadherin, sialic acid and phospholipid, key components of MFGM were significantly positively correlated to Bifidobacterium of stool samples from infants, and stimulated the growth rate of Bifidobacterium significantly by provided energy in vitro growth experiment with RNA analysis. CONCLUSIONS: These findings suggest that the key components from MFGM could improve infants' health by modulating the gut microbiome, and possibly supporting the growth of Bifidobacterium. REGISTRATION: Clinicaltrials.gov NCT02658500 (registered on January 20, 2016).

Influence of Kluyveromyces marxianus on proteins, peptides, and amino acids in Lactobacillus-fermented milk.

With increasing application of yeast in fermented milk, in order to study the effect of yeast on milk protein during the fermentation process, the effects of the presence of Kluyveromyces marxianus in milk fermented by Streptococcus thermophilus and Lactobacillus bulgaricus were investigated. After fermentation, the amino acid, protein, and peptide contents were analyzed by ultra-performance liquid chromatography, two-dimensional gel electrophoresis, and liquid chromatography-mass spectrometry, respectively. After the addition of K. marxianus for fermentation, 25 protein spots changed significantly. These were mostly caseins and bovine serum proteins, and the content of total free amino acids increased by 16.30%; ten types of bioactive peptides were identified. Furthermore, the number of peptide types in milk fermented by K. marxianus increased significantly compared with milk fermented by Lactobacillus. K. marxianus is considered to promote proteometabolism in milk when added with Lactobacillus, generate flavor compounds, and improve the digestion and absorption character of milk.

Synthesis of Cu(I) trifluoromethylselenates for trifluoromethylselenolation of aryl and alkyl halides.

The development of new strategies for synthesis of trifluoromethylthiolate compounds is of considerable importance in pharmaceuticals, agrochemicals, and advanced materials. Accordingly, currently much attention is being devoted to the development of effective methods and reagents for their synthesis. In contrast, considerably less effort has been afforded to the development of preparing CSeCF3 bonds. Herein we report a concise route to synthesize a family of copper(I) trifluoromethylselenolate reagents by the reaction of CuI with the Ruppert's reagent (Me3 SiCF3 ), KF, and elemental selenium in the presence of dinitrogen ligands in CH3 CN at room temperature. The reagent [Cu(bpy)(SeCF3 )]2 was proven to be air-stable and highly efficient for nucleophilic trifluoromethylthselenolation of a broad range of (hetero)aryl halides and alkyl halides. This method represents a powerful protocol for the construction trifluoromethylselenolate compounds.

Performance of remote target pointing hand movements in a 3D environment.

In this study, we investigated and modeled the performance of target pointing hand movements in a hand free, touchless 3D environment. The targets had different positions, sizes and distances. Performance measurements included total movement time and movement trajectories. The total movement time consisted of a "primary submovement time" and a "secondary submovement time". Results indicated that the total movement time for targets with depth in the upper part of the spherical framework (3.10s) was shorter than for targets without depth (3.79s). The time for targets without depth in the lower part of the spherical framework (2.94s) was shorter than for targets with depth (3.57s). Within a 3D perspective display, the perception of distance and size depends on its depth position. Our results confirmed the adequacy of the 3D information in the display by showing the longest total movement time was observed for the reach of the "forward" target (3.94s). Fitts' model explained the total movement time (for targets without depth r(2)=.72; for targets with depth r(2)=.72). This study showed that participants navigated the 3D space naturally and could move the cursor using both sequential a axis moving strategy and a straight line moving strategy. Real-life applications of the proposed method include interface design for 3D perspective displays and hand movements in 3D environments.