Analysis of the Endogenous Peptidomes of Different Infant Formula Types and Human Milk.
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ABSTRACT:
SUBMITTER: Wolk M
PROVIDER: S-EPMC8623676 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBreastfed infants have lower disease risk compared to formula-fed infants, however, the mechanisms behind this protection are unknown. Human milk has a complex lipidome which may have many critical roles in health and disease risk. However, human milk lipidomics is challenging, and research is still required to fully understand the lipidome and to interpret and translate findings. This study aimed to address key human milk lipidome knowledge gaps and discuss possible implications for early life health.MethodsHuman milk samples from two birth cohorts, the Barwon Infant Study (n = 312) and University of Western Australia birth cohort (n = 342), were analysed using four liquid chromatography-mass spectrometry (LC-MS) methods (lipidome, triacylglycerol, total fatty acid, alkylglycerol). Bovine, goat, and soy-based infant formula, and bovine and goat milk were analysed for comparison. Composition was explored as concentrations, relative abundance, and infant lipid intake. Statistical analyses included principal component analysis, mixed effects modelling, and correlation, with false discovery rate correction, to explore human milk lipidome longitudinal trends and inter and intra-individual variation, differences between sample types, lipid intakes, and correlations between infant plasma and human milk lipids.ResultsLipidomics analysis identified 979 lipids. The human milk lipidome was distinct from that of infant formula and animal milk. Ether lipids were of particular interest, as they were significantly higher, in concentration and relative abundance, in human milk than in formula and animal milk, if present in the latter samples at all. Many ether lipids were highest in colostrum, and some changed significantly through lactation. Significant correlations were identified between human milk and infant circulating lipids (40% of which were ether lipids), and specific ether lipid intake by exclusively breastfed infants was 200-fold higher than that of an exclusively formula-fed infant.ConclusionThere are marked differences between the lipidomes of human milk, infant formula, and animal milk, with notable distinctions between ether lipids that are reflected in the infant plasma lipidome. These findings have potential implications for early life health, and may reveal why breast and formula-fed infants are not afforded the same protections. Comprehensive lipidomics studies with outcomes are required to understand the impacts on infant health and tailor translation.
| S-EPMC10499237 | biostudies-literature
Project description:Mammary gland secretory cells produce miRNA-rich milk. In humans, these miRNAs reach infant/neonate bloodstream, playing diverse roles, like neural system development, metabolism, and immune system maturation. Notwithstanding, still few works explore human milk miRNA content, and there are no reports at the population level. Our hypothesis was that miR-146b-5p, miR148a-3p, miR155-5p, mir181a-5p, and mir200a-3p immunoregulatory miRNAs are expressed in human colostrum/milk at a higher level than infant milk formulae. The aim of this work was to evaluate the expression of the five immunoregulatory miRNAs in human milk and compare it with their expression in infant milk formula. For this purpose, miRNA relative expression was measured by qPCR in cDNA prepared from total RNA extracted from sixty human colostrum/milk samples and six different formulae. The comparative Cт method 2−ΔCт using exogenous cel-miR-39 as internal control was employed, followed by statistical analysis. We found the relative expression levels of miRNAs are comparable among colostrum/milk samples, and these miRNAs are present in infant milk formulae but at very low concentrations. We conclude that the relative expression of the immunomodulatory miRNAs is comparable in all the human colostrum/milk samples and is higher than the expression in formulae.
| S-EPMC9264398 | biostudies-literature
Project description:Milk and milk products such as infant formula (IF) play a fundamental role in serving the nutritional needs of the developing infant. Extracellular vesicles (EVs) in human (HM) and cow’s milk (CM) contain molecular cargo such as proteins and micro(mi)RNA that serve as functional messengers between cells and may be of importance to infant health. Here, we have developed a pipeline using advanced proteomics and transcriptomics to enable cross-species comparison of milk and IF EVs. EVs from HM, CM and IF were subjected to data-independent acquisition mass spectrometry and RNA-seq. Differentially abundant proteins (143) and miRNAs (514) (false discovery rate < 0.01) were identified in HM and CM EVs, and CM EV proteins and miRNAs were conserved in IF EVs (~20-90%). We foresee this work to be used in large scale studies to determine biologically relevant species-specific differences in milk EVs that could be leveraged to improve IF products.
2023-08-13 | PXD039923 | Pride
Project description:Intestinal microecology has been shown to participate in the pathogenesis of many diseases through different pathways, and the intestinal microecology of premature infants is significantly different from full-term infants. Intestinal microecology in premature infants is affected by various factors such as gestational age, diet, antibiotic use. However, there are few studies focus on the effects of diet on intestinal microecological development in premature infants. This study explored the different effects of the formula milk (FM) and breast milk (BM) for the development of intestinal microecology in premature infants. The results showed that BM feeding increases the alpha diversity of the intestinal flora, however, FM feeding contributes to the increase in short-chain fatty acids (SCFAs) in the gut of preterm infants. The growth environment has an important influence on the β diversity of intestinal microecology, the genomic function, and the evolution of intestinal microecology in premature infants. The intestinal microecology in premature infants is significantly associated with gestational age and weight gain. This study explored the effects of feeding methods and growth environment on intestinal microecology in premature infants, and provided a basis for promoting the healthy development of premature infants.
| S-EPMC6978717 | biostudies-literature
Project description:BACKGROUND:Early infant diet influences postnatal gut microbial development, which in turn can modulate the developing immune system. OBJECTIVES:The aim of this study was to characterize diet-specific bioregional microbiota differences in piglets fed either human breast milk (HM) or infant formula. METHODS:Male piglets (White Dutch Landrace Duroc) were raised on HM or cow milk formula (MF) from postnatal day (PND) 2 to PND 21 and weaned to an ad libitum diet until PND 51. Piglets were euthanized on either PND 21 or PND 51, and the gastrointestinal contents were collected for 16s RNA sequencing. Data were analyzed using the Quantitative Insight into Microbial Ecology. Diversity measurements (Chao1 and Shannon) and the Wald test were used to determine relative abundance. RESULTS:At PND 21, the ileal luminal region of HM-fed piglets showed lower Chao1 operational taxonomic unit diversity, while Shannon diversity was lower in cecal, proximal colon (PC), and distal colon (DC) luminal regions, relative to MF-fed piglets. In addition, at PND 51, the HM-fed piglets had lower genera diversity within the jejunum, ileum, PC, and DC luminal regions, relative to MF-fed piglets. At PND 21, Turicibacter was 4- to 5-fold lower in the HM-fed piglets' ileal, cecal, PC, and DC luminal regions, relative to the MF-fed piglets. Campylobacter is 3- to 6-fold higher in HM-fed piglets duodenal, ileal, cecal, PC, and DC luminal regions, in comparison to MF-fed piglets. Furthermore, the large intestine (cecum, PC, and rectum) luminal region of HM-fed piglets showed 4- to 7-fold higher genera that belong to class Bacteroidia, in comparison to MF-fed piglets at PND 21. In addition, at PND 51 distal colon lumen of HM-fed piglets showed 1.5-fold higher genera from class Bacteroidia than the MF-fed piglets. CONCLUSIONS:In the large intestinal regions (cecum, PC, and rectum), MF diet alters microbiota composition, relative to HM diet, with sustained effects after weaning from the neonatal diet. These microbiota changes could impact immune system and health outcomes later in life.
| S-EPMC6888031 | biostudies-literature
Project description:Early nutrition plays a dominant role in infant development and health. It is now understood that the infant diet impacts the gut microbiota and its relationship with gut function and brain development. However, its impact on the microbiota-gut-brain axis has not been studied in an integrative way. The objective here was to evaluate the effects of human milk (HM) or cow's milk based infant formula (IF) on the relationships between gut microbiota and the collective host intestinal-brain axis. Eighteen 10-day-old Yucatan mini-piglets were fed with HM or IF. Intestinal and fecal microbiota composition, intestinal phenotypic parameters, and the expression of genes involved in several gut and brain functions were determined. Unidimensional analyses were performed, followed by multifactorial analyses to evaluate the relationships among all the variables across the microbiota-gut-brain axis. Compared to IF, HM decreased the α-diversity of colonic and fecal microbiota and modified their composition. Piglets fed HM had a significantly higher ileal and colonic paracellular permeability assessed by ex vivo analysis, a lower expression of genes encoding tight junction proteins, and a higher expression of genes encoding pro-inflammatory and anti-inflammatory immune activity. In addition, the expression of genes involved in endocrine function, tryptophan metabolism and nutrient transport was modified mostly in the colon. These diet-induced intestinal modifications were associated with changes in the brain tissue expression of genes encoding the blood-brain barrier, endocrine function and short chain fatty acid receptors, mostly in hypothalamic and striatal areas. The integrative approach underlined specific groups of bacteria (Veillonellaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae) associated with changes in the gut-brain axis. There is a clear influence of the infant diet, even over a short dietary intervention period, on establishment of the microbiota-gut-brain axis.
| S-EPMC9532976 | biostudies-literature
Project description:Holistic benefits of human milk to infants, particularly brain development and cognitive behavior, have stipulated that infant formula be tailored in composition like human milk. However, the composition of human milk, especially lipids, and their effects on brain development is complex and not fully elucidated. We evaluated brain lipidome profiles in weanling rats fed human milk or infant formula using non-targeted UHPLC-MS techniques. We also compared the lipid composition of human milk and infant formula using conventional GC-FID and HPLC-ELSD techniques. The sphingomyelin class of lipids was significantly higher in brains of rats fed human milk. Lipid species mainly comprising saturated or mono-unsaturated C18 fatty acids contributed significantly higher percentages to their respective classes in human milk compared to infant formula fed samples. In contrast, PUFAs contributed significantly higher percentages in brains of formula fed samples. Differences between human milk and formula lipids included minor fatty acids such as C8:0 and C12:0, which were higher in formula, and C16:1 and C18:1 n11, which were higher in human milk. Formula also contained higher levels of low- to medium-carbon triacylglycerols, whereas human milk had higher levels of high-carbon triacylglycerols. All phospholipid classes, and ceramides, were higher in formula. We show that brain lipid composition differs in weanling rats fed human milk or infant formula, but dietary lipid compositions do not necessarily manifest in the brain lipidome.
| S-EPMC6918239 | biostudies-literature
Project description:ObjectivesThe aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity.MethodsHealthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk-based infant formula (control, n = 87) or the same formula with 1.0 g/L 2'fucosyllactose (2'FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months.ResultsWeight gain was similar in both groups (mean difference [95% confidence interval] test vs control: -0.30 [-1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [-3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004-0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%).ConclusionsInfant formula with 2'FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies.
| S-EPMC5378003 | biostudies-literature
Project description:We sought to determine whether an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) was tolerated by infants with cow's milk protein allergy (CMPA). A whey-based EHF (Test formula) containing 2'fucosyl-lactose (2'FL) and lacto-N-neotetraose (LNnT) was assessed for clinical hypoallergenicity and safety. The Control formula was a currently marketed EHF without HMO. Children with CMPA, aged 2 months to 4 years, were assessed by double-blind, placebo-controlled food challenges (DBPCFC) to both formulas, in randomized order. If both DBPCFC were negative, subjects participated in a one-week, open food challenge (OFC) with the Test formula. Symptoms and adverse events were recorded. Hypoallergenicity was accepted if at least 90% (with 95% confidence intervals) of subjects tolerated the Test formula. Of the 82 children with CMPA that were screened, 67 (intention-to-treat [ITT] cohort-mean age 24.5 ± 13.6 months; range 2-57; 45 [67.2%] male) were randomized to receive either the Test or the Control formula during the first DBPCFC. Of these, 64 children completed at least one DBPCFC (modified intention-to-treat [mITT] cohort). Three children were excluded due to protocol deviations (per protocol [PP] cohort; n = 61). There was one allergic reaction to the Test, and one to the Control formula. On the mITT analysis, 63 out of 64 (98.4%; 95% CI lower bound 92.8%), and on the PP analysis 60 out of 61 (98.4%; 95% CI lower bound 92.5%) participants tolerated the Test formula, confirming hypoallergenicity. The whey-based EHF supplemented with 2'FL and LNnT met the clinical hypoallergenicity criteria and can be recommended for the management of CMPA in infants and young children.
| S-EPMC6682865 | biostudies-literature
Project description:BackgroundHuman milk oligosaccharides (HMOs) are important components of breast milk and may be responsible for some of the benefits of breastfeeding, including resistance to infections and the development of a healthy gut microbiota. Selected HMOs are now available for addition to infant formula, and suitable methods to control the dosing rate are needed.ObjectiveTo develop and validate a suitable method for the analysis of HMOs in infant formula.MethodA method was developed for the determination of seven human milk oligosaccharides (2'-fucosyllactose, 3-fucosyllactose, 3'-sialyllactose, 6'-sialyllactose (6'SL), 2',3-difucosyllactose, lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT)) in infant formula and adult nutritionals. The oligosaccharides are labeled at their reducing end with 2-aminobenzamide, separated by liquid chromatography and detected using a fluorescence detector. Maltodextrins are enzymatically hydrolyzed before analysis to prevent potential interference; likewise, an optional β-galactosidase treatment can be used to remove β-galactooligosaccharides. Fructooligosaccharides or polydextrose do not generally interfere with the analysis.ResultsThe method has been validated in a single laboratory on infant formula and adult nutritionals. The seven HMOs were spiked into eight matrixes at three or four spike levels, giving a total of 176 data points. Recoveries were in the range of 90.9-109% in all cases except at the lowest spike level in one matrix (elemental formula), where the LNT recovery was 113%, the LNnT recovery was 111%, and the 6'SL recovery was 121%. Relative repeatabilities (RSD(r)) were in the range of 0.1-4.2%. The performance is generally within the requirements outlined in the Standard Method Performance Requirements (SMPR®) published by AOAC INTERNATIONAL.ConclusionsThe method developed is suitable for the determination of seven HMOs in infant formula and demonstrated good performance during single-laboratory validation.HighlightsA method has been developed that is suitable for the determination of seven HMOs in infant formula.
| S-EPMC10907138 | biostudies-literature