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Changes in Proteases, Antiproteases, and Bioactive Proteins From Mother's Breast Milk to the Premature Infant Stomach.

ABSTRACT: OBJECTIVE:Our previous studies suggested that human milk proteases begin to hydrolyze proteins in the mammary gland and continue within the term infant' stomach. No research has measured milk protease and pepsin activity in the gastric aspirates of preterm infants after human milk feeding. This study investigated how the concentrations of human milk proteases and protease inhibitors changed in the premature infant stomach. METHODS:Human milk and infant gastric samples were collected from 18 preterm-delivering mother-infant pairs (24-32 week gestational age). Paired human milk and gastric samples were collected across postnatal age (2-47 days). Protease concentrations were determined by spectrophotometric or fluorometric assays, and the concentrations of protease inhibitors and bioactive proteins were determined by enzyme-linked immunosorbent assay. Paired t tests were applied to compare enzymes, antiproteases, and bioactive proteins between human milk and gastric samples. RESULTS:Our study reveals that although human milk proteases, including carboxypeptidase B2, kallikrein, plasmin, cathepsin D, elastase, thrombin, and cytosol aminopeptidase, are present in the preterm infant stomach, only plasmin and cathepsin D can actively hydrolyze proteins at gastric pH. Enzyme-linked immunosorbent assay and peptidomic evidence suggest that all milk antiproteases as well as lactoferrin and immunoglobulin A are partially digested in the preterm stomach. CONCLUSIONS:Most human milk proteases are active in milk but not at preterm infant gastric pH. Only cathepsin D and plasmin have potential to continue degrading milk proteins within the preterm infant stomach.

SUBMITTER: Demers-Mathieu V

PROVIDER: S-EPMC5780254 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Changes in Proteases, Antiproteases, and Bioactive Proteins From Mother's Breast Milk to the Premature Infant Stomach.

Demers-Mathieu Veronique V Nielsen Søren Drud SD Underwood Mark A MA Borghese Robyn R Dallas David C DC

Journal of pediatric gastroenterology and nutrition 20180201 2

<h4>Objective</h4>Our previous studies suggested that human milk proteases begin to hydrolyze proteins in the mammary gland and continue within the term infant' stomach. No research has measured milk protease and pepsin activity in the gastric aspirates of preterm infants after human milk feeding. This study investigated how the concentrations of human milk proteases and protease inhibitors changed in the premature infant stomach.<h4>Methods</h4>Human milk and infant gastric samples were collect ...[more]

PMID: 28906320

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Project description:BackgroundHuman milk oligosaccharides (HMOs) and bioactive proteins likely benefit infant health, but information on these relations is sparse.ObjectivesWe aimed to examine associations of milk content of HMOs and bioactive proteins with incidence and longitudinal prevalence of infant morbidity (any illness, fever, diarrhea, acute respiratory infection, and loss of appetite) and markers of inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)]. These are secondary analyses of a randomized controlled trial.MethodsBreast milk samples at 6 mo postpartum (n = 659) were analyzed to quantify absolute abundance of HMOs, relative abundance of fucosylated HMOs, sialylated HMOs, and 51 individual HMOs, and concentrations of 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of these constituents with infant morbidity from 6 to 7 and 6 to 12 mo, and CRP and AGP at 6 and 18 mo, considering maternal secretor status [presence or absence of the functional enzyme encoded by the fucosyltransferase 2 gene (FUT2) ] and adjusting for covariates and multiple hypothesis testing.ResultsIn secretors there were positive associations between total HMOs and longitudinal prevalence of fever (P = 0.032), between fucosylated HMOs and incidence of diarrhea (P = 0.026), and between lactoferrin and elevated CRP at 18 mo (P = 0.011). In nonsecretors, there were inverse associations between lactoferrin and incidence of fever (P = 0.007), between osteopontin and longitudinal prevalence of lost appetite (P = 0.038), and between fucosylated HMOs and incidence of diarrhea (P = 0.025), lost appetite (P = 0.019), and concentrations of AGP and CRP at 6 mo (P = 0.001 and 0.010); and positive associations between total HMOs and incidence of lost appetite (P = 0.024) and elevated CRP at 18 mo (P = 0.026), between lactalbumin and incidence of diarrhea (P = 0.006), and between lactoferrin and elevated CRP at 18 mo (P = 0.015).ConclusionsCertain HMOs and bioactive proteins were associated with infant morbidity and inflammation, particularly in nonsecretors. Further research is needed to elucidate the causality of these relations.This trial was registered at clinicaltrials.gov as NCT01239693.

Project description:BackgroundHuman milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries.ObjectivesWe aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi.MethodsBreast milk samples were analyzed at 6 mo (n = 659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing.ResultsAmong all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (P = 0.018 and P = 0.044), and a positive association of lactalbumin concentration with motor skills (P = 0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (P = 0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (P < 0.001 and P = 0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (P = 0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors.ConclusionsCertain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists.This trial was registered at clinicaltrials.gov as NCT01239693.

Dataset Information

Changes in Proteases, Antiproteases, and Bioactive Proteins From Mother's Breast Milk to the Premature Infant Stomach.

Publications

Changes in Proteases, Antiproteases, and Bioactive Proteins From Mother's Breast Milk to the Premature Infant Stomach.

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