Extraction and Quantitative Analysis of Goat Milk Oligosaccharides:Composition, Variation, Associations, and 2 '-FL Variability

Human milk oligosaccharides (hMOS) are associated with health benefits for newborns. We studied the composition of goat MOS (gMOS) from colostrum up to the 9th month of lactation to conceive an overview of the structures present and their fate. Potential correlations with factors such as age, parity, and lifetime milk production were examined. An effective method for gMOS extraction and ultra-high-performance liquid chromatography coupled to fluorescence detection (UPLC-FLD) analysis was established, following 2-aminobenzamide gMOS labeling. Considerable biological variability was highlighted among the 12 quantified gMOS and the 9 non-quantified structures in the individual milk samples. Most characteristic, 2'-fucosyllactose was present in 73.7% of the milk samples analyzed, suggesting the possibility of a secretor/non-secretor goat genotype, similar to humans. Contributing factors to the observed biological variability were goat age, parity, lifetime milk production, and the kids' sex. The results significantly contribute to the current understanding of (variations in) gMOS composition

Biological Relevance of Goat Milk Oligosaccharides to Infant Health

Milk is often regarded as the gold standard for the nourishment of all mammalian offspring. The World Health Organization (WHO) recommends exclusive breastfeeding for the first 6 months of the life of the infant, followed by a slow introduction of complementary foods to the breastfeeding routine for a period of approximately 2 years, whenever this is possible ( Global Strategy for Infant and Young Child Feeding; WHO, 2003). One of the most abundant components in all mammals' milk, which is associated with important health benefits, is the oligosaccharides. The milk oligosaccharides (MOS) of humans and other mammals differ in terms of their concentration and diversity. Among those, goat milk contains more oligosaccharides ( gMOS) than other domesticated dairy animals, as well as a greater range of structures. This review summarizes the biological functions of MOS found in both human and goat milk to identify the possible biological relevance of gMOS in human health and development. Based on the existing literature, seven biological functions of gMOS were identified, namely, MOS action as prebiotics, immune modulators, and pathogen traps; their modulation of intestinal cells; protective effect against necrotizing enterocolitis; improved brain development; and positive effects on stressor exposure. Overall, goat milk is a viable alternate supply of functional MOS that could be employed in a newborn formula. </p

Differential Modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids

Peer reviewe

Time-Resolved and Tissue-Specific Systems Analysis of the Pathogenesis of Insulin Resistance

BACKGROUND: The sequence of events leading to the development of insulin resistance (IR) as well as the underlying pathophysiological mechanisms are incompletely understood. As reductionist approaches have been largely unsuccessful in providing an understanding of the pathogenesis of IR, there is a need for an integrative, time-resolved approach to elucidate the development of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Male ApoE3Leiden transgenic mice exhibiting a humanized lipid metabolism were fed a high-fat diet (HFD) for 0, 1, 6, 9, or 12 weeks. Development of IR was monitored in individual mice over time by performing glucose tolerance tests and measuring specific biomarkers in plasma, and hyperinsulinemic-euglycemic clamp analysis to assess IR in a tissue-specific manner. To elucidate the dynamics and tissue-specificity of metabolic and inflammatory processes key to IR development, a time-resolved systems analysis of gene expression and metabolite levels in liver, white adipose tissue (WAT), and muscle was performed. During HFD feeding, the mice became increasingly obese and showed a gradual increase in glucose intolerance. IR became first manifest in liver (week 6) and then in WAT (week 12), while skeletal muscle remained insulin-sensitive. Microarray analysis showed rapid upregulation of carbohydrate (only liver) and lipid metabolism genes (liver, WAT). Metabolomics revealed significant changes in the ratio of saturated to polyunsaturated fatty acids (liver, WAT, plasma) and in the concentrations of glucose, gluconeogenesis and Krebs cycle metabolites, and branched amino acids (liver). HFD evoked an early hepatic inflammatory response which then gradually declined to near baseline. By contrast, inflammation in WAT increased over time, reaching highest values in week 12. In skeletal muscle, carbohydrate metabolism, lipid metabolism, and inflammation was gradually suppressed with HFD. CONCLUSIONS/SIGNIFICANCE: HFD-induced IR is a time- and tissue-dependent process that starts in liver and proceeds in WAT. IR development is paralleled by tissue-specific gene expression changes, metabolic adjustments, changes in lipid composition, and inflammatory responses in liver and WAT involving p65-NFkB and SOCS3. The alterations in skeletal muscle are largely opposite to those in liver and WAT

Introduction of Heated Cow's Milk Protein in Challenge-Proven Cow's Milk Allergic Children:The iAGE Study

The introduction of baked milk products in cow's milk (CM) allergic children has previously been shown to accelerate induction tolerance in a selected group of children. However, there is no standardized baked milk product on the market. Recently, a new standardized, heated and glycated cow's milk protein (HP) product was developed. The aim of this study was to measure safety and tolerability of a new, well characterized heated CM protein (HP) product in cow's milk allergic (CMA) children between the age of 3 and 36 months. The children were recruited from seven clinics throughout The Netherlands. The HP product was introduced in six incremental doses under clinical supervision. Symptoms were registered after introduction of the HP product. Several questionnaires were filled out by parents of the children. Skin prick tests were performed with CM and HP product, sIgE to CM and α-lactalbumin (Bos d4), β-lactoglobulin (Bos d5), serum albumin (Bos d 6), lactoferrin (Bos d7) and casein (Bos d8). Whereas 72% percent (18 out of 25) of the children tolerated the HP product, seven children experienced adverse events. Risk factors for intolerance to the HP product were higher skin prick test (SPT) histamine equivalent index (HEP) results with CM and the HP product, higher specific IgE levels against Bos d4 and Bos d8 levels and Bos d5 levels. In conclusion, the HP product was tolerated by 72% of the CM allergic children. Outcomes of SPT with CM and the HP product, as well as values of sIgE against caseins, α-lactalbumin, and β-lactoglobulin may predict the tolerability of the HP product. Larger studies are needed to confirm these conclusions.</p

Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status

We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500 ml dairy shake containing respectively 59, 30 and 12 energy percent lipids, carbohydrates and protein. During a 6 h time course after PCT 145 plasma metabolites, 79 proteins and 7 clinical chemistry parameters were quantified. Multiple processes related to metabolism, oxidation and inflammation reacted to the PCT, as demonstrated by changes of 106 metabolites, 31 proteins and 5 clinical chemistry parameters. The PCT was applied in a dietary intervention study to evaluate if the PCT would reveal additional metabolic changes compared to non-perturbed conditions. The study consisted of a 5-week intervention with a supplement mix of anti-inflammatory compounds in a crossover design with 36 overweight subjects. Of the 231 quantified parameters, 31 had different responses over time between treated and control groups, revealing differences in amino acid metabolism, oxidative stress, inflammation and endocrine metabolism. The results showed that the acute, short term metabolic responses to the PCT were different in subjects on the supplement mix compared to the controls. The PCT provided additional metabolic changes related to the dietary intervention not observed in non-perturbed conditions. Thus, a metabolomics based quantification of a standardized perturbation of metabolic homeostasis is more informative on metabolic status and subtle health effects induced by (dietary) interventions than quantification of the homeostatic situation

High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells.

Item does not contain fulltextFolate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12 and other micronutrients involved in the folate-methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism