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Human milk Oligosaccharides (HMOs) are a major component in human milk and recognized to play an important role in modulating gut microbiota, intestinal cell response, and the development of the brain and immune system. While HMOs levels from Chinese mothers across different regions of China have been reported, data from Hebei are lacking. Twelve HMOs were measured from a cross-section of Hebei Han mothers over a 15-month lactation period. The average total of the 12 measured HMOs was 4872 ± 1902 mg/L, similar to that reported for Han mothers from other Chinese regions. Hebei Han mothers had much lower LNnT (59.0 ± 53.1 mg/L), LNFP II (257.5 ± 211.0 mg/L) and LNFP III (149.9 ± 121.7 mg/L) levels and higher 3FL levels (1875.2 ± 1065.3 mg/L) compared to other regional Chinese mother cohorts. The distribution of secretor and Lewis status for this Hebei mother cohort was measured at 68.5 %, 21.9 %, 8.2 % and 1.4 % respectively for Se + Le + , Se - Le + , Se + Le - and Se - Le - respectively. The results from this study suggest that location has influence over the HMOs concentration., Competing Interests: The authors declare they have no conflict of interest. Yibing Ning, Yiping Xun, Huanzhe Dong and Qingbin Yuan are employees of Junlebao Dairy Groups Co. Ltd, China, while Bertram Fong, Paul McJarrow and Lin Ma are employees of Fonterra Dairy Group Ltd, New Zealand. Dr Hamid Jan Jan Mohamed is Professor at the School of Health Sciences, Universiti Sains Malaysia, Malaysia., (© 2024 The Authors.)

Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GM3SD) causes an absence of GM3 and all downstream biosynthetic derivatives, including all the a-, b-, c-series gangliosides, commonly found in neural tissues. The affected individuals manifest with severe irritability, intractable seizures, hearing loss, blindness, and profound intellectual disability. It has been reported that oral ganglioside supplementation has achieved some significant improvements in clinical symptoms, growth parameters, and developmental and cognitive scores in GM3SD patients. To gain insight into the molecular mechanisms of this supplementation, we performed supplementation of oral bovine milk gangliosides to GM3 synthase-deficient mice from early weaning periods. The oral milk ganglioside preparations were dominated by GM3 and GD3 gangliosides. Oral milk ganglioside supplementation improved the decreased cognitive function observed in GM3 synthase-deficient mice. The improvement in cognitive function was accompanied by increased ganglioside levels and neurogenesis in the hippocampus in the supplemented animals., 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. The authors declare that this study received funding from Fonterra co-operative Group Ltd. The funder had the following involvement in the study: study design, analysis and interpretation of data, the writing of this article and the decision to submit it for publication., (Copyright © 2024 Inokuchi, Go, Suzuki, Nakagawasai, Odaira-Satoh, Veillon, Nitta, McJarrow, Kanoh, Inamori, Tan-No and Collett.)

Gangliosides are glycosphingolipids present in mammalian cell membranes, playing important structural and functional roles. Human studies on the health benefits of gangliosides are increasing, but knowledge gaps regarding ganglioside analysis exist. The study aimed to investigate blood sample type (serum/plasma), storage conditions, diurnal, day-to-day variation and acute effects of consuming bovine-derived gangliosides on circulating monosialylated gangliosides. Seventy-one women (18-40 yrs, 20-≤30.0 kg/m 2 ) were enrolled and 61 completed the intervention. They visited the clinic three times following overnight fasting. Serum/plasma gangliosides were analyzed over 2 h (visit-1), 8 h (visit-2) and 8 h following either zero or high ganglioside meals (visit-3). Samples stored at -20 °C and -70 °C were analyzed at 3-, 6-, 12- and 18-months. Plasma and serum GM3-gangliosides did not differ, plasma GM3 did not change diurnally, from day-to-day, in response to a high vs. low ganglioside meal or after 7-days low ganglioside vs. habitual diet ( P > 0.05). GM3 concentrations were lower in samples stored at -70 °C vs. -20 °C from 6-months onwards and decreased over time with lowest levels at 12- and 18-months stored at -70 °C. In conclusion, either serum/plasma stored at -20- or -70 °C for up to 6 months, are acceptable for GM3-ganglioside analysis. Blood samples can be collected at any time of the day and participants do not have to be in the fasted state.

Human milk oligosaccharides (HMOs), phospholipids (PLs), and gangliosides (GAs) are components of human breast milk that play important roles in the development of the rapidly growing infant. The differences in these components in human milk from the United Arab Emirates (UAE) were studied in a cross-sectional trial. High-performance liquid chromatography‒mass spectrometry was used to determine HMO, PL, and GA concentrations in transitional (5-15 days) and mature (at 6 months post-partum) breast milk of mothers of the United Arab Emirates (UAE). The results showed that the average HMO (12 species), PL (7 species), and GA (2 species) concentrations quantified in the UAE mothers' transitional milk samples were (in mg/L) 8204 ± 2389, 269 ± 89, and 21.18 ± 11.46, respectively, while in mature milk, the respective concentrations were (in mg/L) 3905 ± 1466, 220 ± 85, and 20.18 ± 9.75. The individual HMO concentrations measured in this study were all significantly higher in transitional milk than in mature milk, except for 3 fucosyllactose, which was higher in mature milk. In this study, secretor and non-secretor phenotype mothers showed no significant difference in the total HMO concentration. For the PL and GA components, changes in the individual PL and GA species distribution was observed between transitional milk and mature milk. However, the changes were within the ranges found in human milk from other regions.

Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GM3D) causes an absence of GM3 and all downstream biosynthetic derivatives. The affected individuals manifest with severe irritability, intractable seizures, and profound intellectual disability. The current study is to assess the effects of an oral ganglioside supplement to patients with GM3D, particularly on their growth and development during early childhood. A total of 13 young children, 11 of them under 40 months old, received oral ganglioside supplement through a dairy product enriched in gangliosides, for an average of 34 months. Clinical improvements were observed in most children soon after the supplement was initiated. Significantly improved growth and development were documented in these subjects as average percentiles for weight, height, and occipitofrontal circumference increased in 1-2 months. Three children with initial microcephaly demonstrated significant catch-up head growth and became normocephalic. We also illustrated brief improvements in developmental and cognitive scores, particularly in communication and socialization domains through Vineland-II. However, all improvements seemed transient and gradually phased out after 12 months of supplementation. Gangliosides GM1 and GM3, although measureable in plasma during the study, were not significantly changed with ganglioside supplementation for up to 30 months. We speculate that the downstream metabolism of ganglioside biosynthesis is fairly active and the potential need for gangliosides in the human body is likely substantial. As we search for new effective therapies for GM3D, approaches to reestablish endogenous ganglioside supplies in the affected individuals should be considered.

Background: The milk fat globule membrane (MFGM) is primarily composed of polar phospho- and sphingolipids, which have established biological effects on neuroplasticity. The present study aimed to investigate the effect of dietary MFGM supplementation on the neuromuscular system during post-natal development., Methods: Growing rats received dietary supplementation with bovine-derived MFGM mixtures consisting of complex milk lipids (CML), beta serum concentrate (BSC) or a complex milk lipid concentrate (CMLc) (which lacks MFGM proteins) from post-natal day 10 to day 70., Results: Supplementation with MFGM mixtures enriched in polar lipids (BSC and CMLc, but not CML) increased the plasma phosphatidylcholine (PC) concentration, with no effect on plasma phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatidylserine (PS) or sphingomyelin (SM). In contrast, muscle PC was reduced in rats receiving supplementation with both BSC and CMLc, whereas muscle PI, PE, PS and SM remained unchanged. Rats receiving BSC and CMLc (but not CML) displayed a slow-to-fast muscle fibre type profile shift (MyHCI → MyHCIIa) that was associated with elevated expression of genes involved in myogenic differentiation (myogenic regulatory factors) and relatively fast fibre type specialisation ( Myh2 and Nfatc4 ). Expression of neuromuscular development genes, including nerve cell markers, components of the synaptogenic agrin-LRP4 pathway and acetylcholine receptor subunits, was also increased in muscle of rats supplemented with BSC and CMLc (but not CML)., Conclusions: These findings demonstrate that dietary supplementation with bovine-derived MFGM mixtures enriched in polar lipids can promote neuromuscular development during post-natal growth in rats, leading to shifts in adult muscle phenotype.

The most abundant ganglioside group in both human milk and bovine milk during the first postnatal week is ganglioside GD3. This group of disialogangliosides forms up to 80% of the total ganglioside content of colostrum. Although dietary gangliosides have shown biological activity such as improvement of cognitive development, gastrointestinal health, and immune function, there is still a gap in our understanding of the molecular mechanisms governing its uptake and the metabolic processes affecting its bioavailability. The use of isotopically labeled ganglioside to track the bioavailability, absorption, distribution, and metabolism of gangliosides may provide key information to bridge this gap. However, isotope labeled GD3 is not commercially available and its preparation has not been described. We report for the first time the preparation of labeled GD3 with stable isotopes. Using alkaline hydrolysis, we were able to selectively remove both acetyl groups from the tetrasaccharide portion of GD3 without promoting significant hydrolysis of the ceramide portion of the molecule to generate N-deacetyl-GD3 (Neu5α2-8Neu5-GD3). The N-deacetyl-GD3 was then chemoselectively re-acetylated in aqueous medium using deuterated acetic anhydride in the presence of Triton X 100 to produce 2 H 6 -GD3 {GD3[(Neu5Ac-11- 2 H 3 )-(Neu5Ac-11- 2 H 3 )]}. This method provided 2 H 6 -GD3 with approximately 60% yield. This compound was characterized by proton nuclear magnetic resonance ( 1 H NMR) and liquid chromatography mass spectrometry (LC-MS). The oral absorption of the 2 H 6 -GD3 was demonstrated using a Sprague-Dawley weaning rats. Our results indicate that some ingested labeled milk gangliosides are absorbed and transported into the bloodstream without modification., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We have previously reported that the supplementation of ganglioside-enriched complex-milk-lipids improves cognitive function and that a phospholipid-enriched complex-milk-lipid prevents age-related cognitive decline in rats. This current study evaluated the effects of post-natal supplementation of ganglioside- and phospholipid-enriched complex-milk-lipids beta serum concentrate (BSC) on cognitive function in young rats. The diet of male rats was supplemented with either gels formulated BSC (n = 16) or blank gels (n = 16) from post-natal day 10 to day 70. Memory and anxiety-like behaviors were evaluated using the Morris water maze, dark-light boxes, and elevated plus maze tests. Neuroplasticity and white matter were measured using immunohistochemical staining. The overall performance in seven-day acquisition trials was similar between the groups. Compared with the control group, BSC supplementation reduced the latency to the platform during day one of the acquisition tests. Supplementation improved memory by showing reduced latency and improved path efficiency to the platform quadrant, and smaller initial heading error from the platform zone. Supplemented rats showed an increase in striatal dopamine terminals and hippocampal glutamate receptors. Thus BSC supplementation during post-natal brain development improved learning and memory, independent from anxiety. The moderately enhanced neuroplasticity in dopamine and glutamate may be biological changes underlying the improved cognitive function.

Gangliosides are important components of neuronal cell membranes and it is widely accepted that they play a critical role in neuronal and brain development. They are functionally involved in neurotransmission and are thought to support the formation and stabilization of functional synapses and neural circuits required as the structural basis of memory and learning. Available evidence, as reviewed herein, suggests that dietary gangliosides may impact positively on cognitive functions, particularly in the early postnatal period when the brain is still growing. Further, new evidence suggests that the mechanism of action may be through an effect on the neuroplasticity of the brain, mediated through enhanced synaptic plasticity in the hippocampus and nigro-striatal dopaminergic pathway.

Complex milk lipids (CMLs) provide a critical nutritional source for generating both energy and essential nutrients for the growth of the newborn. The present study investigated nutritional supplementation with a CML containing gangliosides and phospholipids in pregnant and lactating rats on learning behavior and postnatal growth in male offspring. Wistar female rats were supplemented during pregnancy and lactation with either control or CML to provide gangliosides at a dose of 0.01% (low) and 0.05% (high) based on total food intake. The CML-supplemented dams showed no differences in comparison to controls regarding growth, food intake, and litter characteristics. There were significant differences in brain composition in male offspring at postnatal day 2 (P2) with higher concentrations of gangliosides (high dose, P < .05) and lower concentrations of phospholipids (low and high dose, P < .05) in the CML-supplemented groups. The distribution of individual ganglioside species was not significantly different between treatment groups. Brain weight at P2 was also significantly higher in the CML groups. Differences in the brain composition and weight were not significant by weaning (P21). As adults (P80), adiposity was reduced in the low CML-supplemented group compared to controls. No significant differences were detected between any of the treatment groups in any of the behavioral tasks (water maze, object recognition, and operant learning). These data suggest that maternal supplementation with a CML during pregnancy and lactation is safe and has a significant early impact on brain weight and ganglioside and phospholipid content in offspring but did not alter long-term behavioral function using standard behavioral techniques., (Copyright 2010 Elsevier Inc. All rights reserved.)

Gangliosides are sialic acid-containing glycosphingolipids. Gangliosides are found in human milk; understanding of the potential role of gangliosides in infant development is emerging, with suggested roles in the brain and gut. Ganglioside accretion in the developing brain is highest in utero and in early neonatal life, during the periods of dendritic branching and new synapse formation. Further, brain contains the highest relative ganglioside content in the body, particularly in neuronal cell membranes concentrated in the area of the synaptic membrane. Gangliosides are known to play a role in neuronal growth, migration and maturation, neuritogenesis, synaptogenesis, and myelination. In addition to their roles in development and structure of the brain, gangliosides also play a functional role in nerve cell communication. It is less well known whether dietary gangliosides can influence the development of cognitive function. This review summarizes current knowledge on the role gangliosides play in brain development.

Alterations in nutritional factors during early development can exert long-term effects on growth, neural function, and associated behaviors. The lipid component of milk provides a critical nutritional source for generating both energy and essential nutrients for the growth of the newborn. The present study, therefore, investigated the hypothesis that nutritional supplementation with a complex milk lipid (CML) preparation, derived from the milk fat globule membrane rich in phospholipids and gangliosides from young rats, has beneficial effects on learning behavior and postnatal growth and development. Male Wistar rat offspring from normal pregnancies were treated from neonatal day 10 until postnatal day 80 with either vehicle or CML at a dose of 0.2% (low) and 1.0% (high) based on total food intake (n = 16 per group). Neonatal dosing was via daily oral gavage, while postweaning dosing was via gel supplementation to a standard chow diet. Animals underwent behavioral tasks related to spatial memory, learning, and cognitive function. Complex milk lipid supplementation significantly increased linear growth rate (P < .05), and the improved growth trajectory was not related to changes in body composition as quantified by dual-energy x-ray absorptiometry scanning or altered plasma lipid profiles. Moreover, this effect was not dose dependent and not attributable to the contribution to total energy intake of the CML composition. Supplementation of the CML to growing rats resulted in statistically significant improvements in parameters related to novelty recognition (P < .02) and spatial memory (P < .05) using standard behavioral techniques, but operant testing showed no significant differences between treatment groups. Supplementation with a CML containing gangliosides had positive growth and learning behavioral effects in young normal growing rats.

The viability of lactic acid bacteria in frozen, freeze-dried, and air-dried forms is of significant commercial interest to both the dairy and food industries. In this study we observed that when prestressed with either heat (50 degrees C) or salt (0.6 M NaCl), Lactobacillus rhamnosus HN001 (also known as DR20) showed significant (P < 0.05) improvement in viability compared with the nonstressed control culture after storage at 30 degrees C in the dried form. To investigate the mechanisms underlying this stress-related viability improvement in L. rhamnosus HN001, we analyzed protein synthesis in cultures subjected to different growth stages and stress conditions, using two-dimensional gel electrophoresis and N-terminal sequencing. Several proteins were up- or down-regulated after either heat or osmotic shock treatments. Eleven proteins were positively identified, including the classical heat shock proteins GroEL and DnaK and the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, enolase, phosphoglycerate kinase, and triose phosphate isomerase, as well as tagatose 1,6-diphosphate aldolase of the tagatose pathway. The phosphocarrier protein HPr (histidine-containing proteins) was up-regulated in cultures after the log phase irrespective of the stress treatments used. The relative synthesis of an ABC transport-related protein was also up-regulated after shock treatments. Carbohydrate analysis of cytoplasmic contents showed higher levels (20 +/- 3 microg/mg of protein) in cell extracts (CFEs) derived from osmotically stressed cells than in the unstressed control (15 +/- 3 microg/mg of protein). Liquid chromatography of these crude carbohydrate extracts showed significantly different profiles. Electrospray mass spectrometry analysis of CFEs revealed, in addition to normal mono-, di-, tri-, and tetrasaccharides, the presence of saccharides modified with glycerol.