Project description:The aim of this study was to investigate how the human milk proteome relates to allergy of the mother and allergy development in the infant.
Project description:The majority of babies in the US are formula-fed instead of breast fed. There are major differences in the composition of formulas and breast milk and yet little is known about metabolic differences in babies as the result of feeding these very different diets and how that might affect development or disease risk in later life. One concern is that soy-based formulas might have adverse health effects in babies as a result of the presence of low levels of estrogenic phytochemicals genistein and daidzein which are normally present in soy beans. In the current study, we used a piglet model to look at this question. Piglets were either fed breast milk from the sow or were fed two different infant formulas (cow's milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food. Blood glucose and lipids were measured. Formula-fed pigs were found to have lower cholesterol than breast fed piglets and in addition had larger stores of iron in their liver.Microarray analysis was carried out to see if changes in liver gene expression could explain these effects of formula feeding. It was found that overall gene expression profiles were influenced by formula feeding compared to breast fed neonates. Gender-independent and unique effects of formula influenced cholesterol and iron metabolism. Further, soy formula feeding in comparison to milk-based formula failed to reveal any estrogenic actions on hepatic gene expression in either male or female pigs. Piglets (female, male) were either fed breast milk from the sow or were fed two different infant formulas (cow's milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food.
Project description:This study was conducted in order to gain insight into microbial and functional differences related to outgrowth of cow’s milk allergy (CMA) and a nutritional intervention with synbiotics.
Project description:Exclusively breast-fed infants can exhibit clear signs of IgE or non IgE-mediated cow’s milk allergy. The definite characterization of dietary cow’s milk proteins (CMP) that survive the maternal digestive tract to be absorbed into the bloodstream and secreted into breast milk remains missing. The aim of this study was to assess the occurrence of CMP-derived peptides in breast milk, using antibody-independent methods. Using high performance liquid chromatography-high resolution mass spectrometry in blinded assays, we identified 11 cow’s milk-derived peptides, including two β-lactoglobulin (2 out 6 samples) and one αs1-casein (1 out 6 samples) fragments, in breast milk from mothers receiving a cup of bovine milk daily. The β-lactoglobulin (β-Lg) fragments, namely f42-54 and f42-57, were absent in milk from mothers who observed a strict dairy-free diet (6 samples). In contrast, neither intact nor hydrolyzed β-Lg was detected by Western blot or competitive ELISA tests. CMP-derived peptides rather than intact CMP may sensitize or elicit allergic responses in the neonate through mother’s milk. Immunologically active peptides from the maternal diet could be involved in priming the newborn’s immune system to drive tolerogenic response in neonates and infants.
Project description:Exclusively breast-fed infants can exhibit clear signs of IgE or non IgE-mediated cow’s milk allergy. The definite characterization of dietary cow’s milk proteins (CMP) that survive the maternal digestive tract to be absorbed into the bloodstream and secreted into breast milk remains missing. The aim of this study was to assess the occurrence of CMP-derived peptides in breast milk, using antibody-independent methods. Using high performance liquid chromatography-high resolution mass spectrometry in blinded assays, we identified 11 cow’s milk-derived peptides, including two ?-lactoglobulin (2 out 6 samples) and one ?s1-casein (1 out 6 samples) fragments, in breast milk from mothers receiving a cup of bovine milk daily. The ?-lactoglobulin (?-Lg) fragments, namely f42-54 and f42-57, were absent in milk from mothers who observed a strict dairy-free diet (6 samples). In contrast, neither intact nor hydrolyzed ?-Lg was detected by Western blot or competitive ELISA tests. CMP-derived peptides rather than intact CMP may sensitize or elicit allergic responses in the neonate through mother’s milk. Immunologically active peptides from the maternal diet could be involved in priming the newborn’s immune system to drive tolerogenic response in neonates and infants.
Project description:<h4><strong>BACKGROUND: </strong>IgE-mediated cow's milk allergy (IgE-CMA) is one of the first allergies to arise in early childhood and may result from exposure to various milk allergens, of which β-lactoglobulin (BLG) and casein are the most important. Understanding the underlying mechanisms behind IgE-CMA is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies.</h4><h4><strong>METHODS: </strong>We report a longitudinal <em>in vivo</em> murine model, in which two mice strains (BALB/c and C57Bl/6) were sensitized to BLG using either cholera toxin or an oil emulsion (n = 6 per group). After sensitization, mice were challenged orally, their clinical signs monitored, antibody (IgE and IgG1) and cytokine levels (IL-4 and IFN-γ) measured, and fecal samples subjected to metabolomics. The results of the murine models were further extrapolated to fecal microbiome-metabolome data from our population of IgE-CMA (n = 22) and healthy (n = 23) children (Trial: NCT04249973), on which polar metabolomics, lipidomics and 16S rRNA metasequencing were performed. In vitro gastrointestinal digestions and multi-omics corroborated the microbial origin of proposed metabolic changes.</h4><h4><strong>RESULTS: </strong>During mice sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid, energy and tryptophan metabolites, that preceded allergic inflammation. We confirmed microbial dysbiosis, and its associated effect on metabolic alterations in our patient cohort, through <em>in vitro</em> digestions and multi-omics, which was accompanied by metabolic signatures of low-grade inflammation.</h4><h4><strong>CONCLUSION: </strong>Our results indicate that gut dysbiosis precedes allergic inflammation and nurtures a chronic low-grade inflammation in children on elimination diets, opening important new opportunities for future prevention and treatment strategies.</h4>