
David Charles DallasOregon State University | OSU · College of Health, Nutrition Program
David Charles Dallas
Ph.D.
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97
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Introduction
Research on how proteins are digested in premature infants
Additional affiliations
Education
September 2008 - June 2012
August 2004 - June 2008
Publications
Publications (97)
Although whey protein isolate (WPI) has been shown to be immunomodulatory, its ability to modulate production of a broad array of inflammatory markers has not previously been investigated in healthy adults. We investigated the effects of daily supplementation with 35 g of WPI for 3 weeks on inflammatory marker concentrations in the blood serum and...
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder marked by chronic abdominal pain, bloating, and irregular bowel habits. Effective treatments are still actively sought. Kappa-casein glycomacropeptide (GMP), a milk-derived peptide, holds promise because it can modulate the gut microbiome, immune responses, gut motility, and barri...
Partial digestion of milk proteins leads to the formation of numerous bioactive peptides. Previously, our research team thoroughly examined the decades of existing literature on milk bioactive peptides across species to construct the milk bioactive peptide database (MBPDB). Herein, we provide a comprehensive update to the data within the MBPDB and...
Background:
Donor human milk banks use Holder pasteurization (62.5 ºC, 30 min) to reduce pathogens in donor human milk, but this process damages some bioactive milk proteins.
Objective:
We aimed to determine minimal parameters for high-pressure processing (HPP) to achieve >5-log reductions of relevant bacteria in human milk and how these paramet...
Bitterness is a common flavor attribute of aged cheese associated with the peptide fraction, but excessive levels are a defect leading to consumer rejection. Bitterness in cheese has been primarily associated with peptides that arise from the breakdown of casein. The last review of bitter peptides was published in 1992. This updated review compiled...
Human milk is universally recognized as the preferred food for infants during the first 6 mo of life because it provides not only essential and conditionally essential nutrients in necessary amounts but also other biologically active components that are instrumental in protecting, communicating important information to support, and promoting optima...
Kappa-casein-derived caseinomacropeptide (CMP)—a 64-amino-acid peptide—is released from kappa-casein after rennet treatment and is one of the major peptides in whey protein isolate (WPI). CMP has anti-inflammatory and antibacterial activities. It also has two major amino acid sequences with different modifications, including glycosylation, phosphor...
Background
Donor human milk should be processed to guarantee microbiological safety prior to infant feeding, but this process can influence the structure and quantity of functional proteins.
Objective
The aim of this study was to determine the effect of thawing, homogenization, vat-pasteurization (Vat-PT), retort sterilization (RTR) and ultra-high...
Background and aims
Plasmin in human milk partially hydrolyzes milk proteins within the mammary gland and may enhance the hydrolysis of milk proteins within the infant’s stomach. This study examined the effects of extremely preterm (EP)-, very preterm (VP)-, and term-delivery on plasmin activity and the concentrations of plasminogen activators [uro...
The ability of bovine κ-casein-derived caseinomacropeptide (CMP) to exert bioactivity in the human gut depends on its digestive survival. Sampling from the human jejunum after feeding CMP and top-down glycopeptidomics analysis facilitates the determination of CMP survival. To reduce interference from non-target molecules in mass spectrometric analy...
Human milk-protein-derived peptides exhibit an array of bioactivities. Certain bioactivities cannot be exerted unless the peptides are absorbed across the gastrointestinal lumen into the bloodstream. The purpose of study was to determine which peptides derived from in vitro digestion of human milk could cross human intestinal Caco-2 cell monolayers...
Background
Bovine milk κ-casein-derived caseinomacropeptide (CMP) is produced in large quantities during cheesemaking and has various biological activities demonstrated via in vitro and in vivo experiments. Previous studies examined protein degradation and peptide release after casein or whey protein consumption. However, whether purified intact CM...
Background
Milk proteins contain many encrypted bioactive peptides. Whether these bioactive peptides are released in the infant intestine and exert immunomodulatory activity remains unknown.
Objective
This study examined in vitro immunomodulatory activities of peptides from in vitro- and in vivo-digested human milk.
Methods
Peptides were extracte...
Background:
Though human milk feeding reduces the risk of necrotizing enterocolitis (NEC) in preterm infants compared with formula feeding, the exact risk reduction mechanism remains unknown. As NEC occurs at the distal small intestines where digestion has occurred, we applied proteomics to examine the extent to which colostrum proteins survive si...
Caseinomacropeptide (CMP) is released from bovine kappa-casein after rennet treatment and is one of the major peptides in whey protein isolate. CMP has in vitro anti-inflammatory and antibacterial activities. CMP has two major amino acid sequences with different modifications, including glycosylation, phosphorylation and oxidation. However, no prev...
Human milk contains numerous N-glycoproteins with functions that provide protection to the infant. Increasing understanding of the functional role of human milk glycoproteins within the infant requires toolsets to comprehensively profile their site-specific glycosylation patterns. However, optimized methods for site-specific glycosylation analysis...
For bioactive milk peptides to be relevant to infant health, they must be released by gastrointestinal proteolysis and resist further proteolysis until they reach their site of activity. The intestinal tract is the likeliest site for most bioactivities, but it is currently unknown whether bioactive milk peptides are present therein. The purpose of...
Aside from their amino acid content, dairy proteins are valuable for their ability to carry encrypted bioactive peptides whose activities are latent until released by digestive enzymes or endogenous enzymes within the food. Peptides can possess a wide variety of functionalities, such as antibacterial, antihypertensive, and antioxidative properties,...
Modern mammalian milk has evolved over more than 200 million years to optimally nourish the infant (Oftedal, J Mammary Gland Biol Neoplasia 7(3):225–252, 2002; Lefèvre et al., Annu Rev Genomics Hum Genet 11(1):219–238, 2010Q2). Milk provides the infant with essential nutrients, including high quality proteins, lipids and carbohydrates, as well as m...
Beyond proteins, milk contains an array of smaller nitrogen (N)-containing components generally referred to as nonprotein nitrogen (NPN). These include milk protein–derived peptides, peptide hormones, amino acids (AAs), N-containing oligosaccharides, N-containing monosaccharides, nucleic acids (DNA and RNA), free nucleotides, and small molecules, i...
The article “Understanding the effects of dietary components on the gut microbiome and human health”, written by Bryna Rackerby, Hyun Jung Kim, David C. Dallas, Si Hong Park, was originally published Online First without Open Access.
Background
Potentially, orally administered antibodies specific to enteric pathogens could be administered to infants to prevent diarrheal infections, particularly in developing countries where diarrhea is a major problem. However, to prevent infection, such antibodies would need to resist degradation within the gastrointestinal tract.
Methods
Pal...
Breast milk contains bile salt-stimulated lipase (BSSL), which significantly increases the fat digestion capacity of newborns who have limited pancreatic lipase secretion in the first few months after birth. Problematically, Holder pasteurization used in non-profit milk banks to ensure the microbiological safety of donor milk for infants, particula...
Our previous studies revealed that milk proteases begin to hydrolyze proteins in the mammary gland and that proteolytic digestion continues within the infant stomach. No research has measured how the release of milk peptides differs between the gastric aspirates of term and premature infants. This study examined the presence of milk peptides in mil...
The gut microbiome is the complex microbial ecosystem found in the gastrointestinal tract of humans and animals. It plays a vital role in host development, physiology and metabolism, and has been implicated as a factor in brain function, behavior, mental health, and many disease states. While many factors, including host genetics and environmental...
Oral administration of engineered immunoglobulins has the potential to prevent enteric pathogen-induced diarrhea in infants. To prevent infection, these antibodies need to survive functionally intact in the proteolytic environment of the gastrointestinal tract. This research examined both ex vivo and in vivo the functional survival across infant di...
Background and aims
Preterm infants are born with a gastrointestinal tract insufficiently developed to digesting large quantities of human milk proteins. Peptides released from the digestion of human milk proteins have been identified with bioactivities that may be beneficial to the developing infant. However, it is unknown how prematurity affects...
Oral administration of enteric pathogen-specific immunoglobulins may be an ideal approach for preventing infectious diarrhea in infants and children. For oral administration to be effective, antibodies must survive functionally intact within the highly proteolytic digestive tract. As an initial step toward assessing the viability of this approach,...
To help rationally design an antibody for oral administration, we examined how different isotypes (IgG, IgA and sIgA) with the same variable sequence affect antibody stability across digestion. We compared the degradation of recombinant palivizumab (IgG1), and recombinant IgA and sIgA versions of palivizumab spiked in human milk to the degradation...
Oral administration of pathogen-specific recombinant antibodies may help to prevent infant gastrointestinal (GI) pathogen infection; however, to neutralize an infectious agent, these antibodies must resist degradation in the GI tract. Palivizumab, a recombinant antibody specific for the respiratory syncytial virus (RSV), was used as a model for pat...
Orally delivered antibodies may be useful for the prevention of enteric pathogen infection, but to be effective they need to survive intact across digestion through the gastrointestinal tract. As a test case, we fed a recombinant human antibody, palivizumab, spiked into human milk to four infants and collected gastric, intestinal and stool samples....
The survival of antibody isotypes specific to pertussis toxin (PT) and filamentous hemagglutinin (FHA) from mother’s own milk (MBM) and donor breast milk (DBM) during preterm infant digestion was investigated.
Feed, gastric, and stool samples were collected from 20 preterm mother–infant pairs at 8–9 days and 21–22 days postpartum. Samples were anal...
Immunomodulatory proteins from human milk may enhance the protection and development of the infant's gut. This study compared the immunomodulatory effects of treatment with milk from preterm-(PM) and term-delivering (TM) mothers and pasteurized donor milk (DM) on cytokine gene expression in human macrophage-like cells derived from the monocytic cel...
To prevent infectious diarrhea in infants, orally-supplemented enteric pathogen-specific recombinant antibodies would need to resist degradation in the gastrointestinal tract. Palivizumab, a recombinant antibody specific to respiratory syncytial virus (RSV), was used as a model to assess the digestion of neutralizing antibodies in infant digestion....
Background:
Human milk peptides released by gastrointestinal proteases have been identified with bioactivities that can benefit the infant but must first reach their respective sites of activity. Peptides in the stool either survived to or were released inside the intestinal tract, and thus had the opportunity to exert bioactivity there. However,...
During digestion, human lactoferrin peptides are released by the action of milk, gastric, and intestinal proteases. Some of these peptides are bioactive, but must be released and survive further digestion until they reach their site of activity in the stomach or intestine. In order to create a map of which lactoferrin peptides are present at which...
Consumption of mothers' milk is associated with reduced incidence and severity of enteric infections, leading to reduced morbidity in breastfed infants. Fucosylated and sialylated human milk oligosaccharides (HMO) are important for both direct antimicrobial action - likely via a decoy effect - and indirect antimicrobial action through commensal gro...
Antenatal milk anti-influenza antibodies may provide additional protection to newborns until they are able to produce their own antibodies. To evaluate the relative abundance of milk, we studied the antibodies specific to influenza A in feeds and gastric contents and stools from preterm infants fed mother’s own breast milk (MBM) and donor breast mi...
Nationally representative data from mother-child dyads that capture human milk composition (HMC) and associated health outcomes are important for advancing the evidence to inform federal nutrition and related health programs, policies, and consumer information across the governments in the United States and Canada as well as in nongovernment sector...
Maternal antibody transfer to the newborn provides essential support for the infant’s naïve immune system. Preterm infants normally receive maternal antibodies through mother’s own breast milk (MBM) or, when mothers are unable to provide all the milk required, donor breast milk (DBM). DBM is pasteurized and exposed to several freeze–thaw cycles, wh...
Digestion of milk proteins in the premature infant stomach releases functional peptides; however, which peptides are present has not been reported. Premature infants are often fed a combination of human milk and bovine milk fortifiers, but the variety of functional peptides released from both human and bovine milk proteins remains uncharacterized....
The complete list of peptides identified in the HMF, milk, and gastric samples.
Sequence lists the peptide sequence. Species lists the peptide's parent protein species. Protein Name lists the parent protein. Start and Stop list the amino acid position the peptide is derived from in the parent protein. HMF, Milk, and Gastric list the number of sampl...
Background:
Human milk immunoglobulins (Ig) are an important support for the naïve infant immune system; yet the extent to which these proteins survive within the infant digestive tract, particularly for preterm infants, is poorly studied.
Objectives:
Our objective was to evaluate the survival of human milk Igs in the preterm stomach across post...
Human milk provides immunoglobulins (Igs) that supplement the passive immune system of neonates; however, the extent of survival of these Igs during gastric digestion and whether this differs between preterm and term infants remains unknown.
Human milk, and infant gastric samples at 2 h post-ingestion were collected from 15 preterm (23–32 week ge...
Human milk and dairy products are important parts of human nutrition. In addition to supplying nutrients, milk proteins contain fragments—peptides—with important biological functions that are released during processing or digestion. Besides their potential functional relevance, peptides released during processing can be used as markers of ripening...
Sodium caseinate hydrolysates (NaCaH) contain biologically active peptides that can positively influence human health. However, their intense bitterness hinders their inclusion in food products. To our knowledge, no studies have investigated whether a correlation between bitterness and bioactivity exists in NaCaH, so it is not yet known what effect...
Aim:
This study investigated the effect of time post-ingestion on gastric digestion and gastric hormones after feeding preterm infants unfortified and fortified human milk.
Methods:
Human milk and infant gastric samples were collected from 14 preterm (23-32 wk birth gestational age) mother-infant pairs within 7-98 days postnatal age. Gastric sam...
Previous work demonstrates that proteases present in human milk release hundreds of peptides derived from milk proteins. However, the question of whether human milk protein digestion begins within the mammary gland remains incompletely answered. The primary objective of this study was to determine whether proteolytic degradation of human milk prote...
Human milk contains active proteases that initiate hydrolysis of milk proteins within the mammary gland. Milk expressed at the beginning of feeding is known as foremilk and that at the end of feeding is known as hindmilk. As hindmilk contains higher fat, vitamins A and E, and higher calories than foremilk, feeding only hindmilk initially and reserv...
Objectives:
Whether premature infants have lower gastric protein digestive capacity than term infants and the extent to which human milk proteases contribute to overall gastric digestion are unknown and were investigated in this study.
Methods:
Human milk and infant gastric samples were collected from 16 preterm (24-32 wk gestational age (GA)) a...
Objectives:
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 m...
Practical applications:
The developed food-grade fractionation system, allowed for a simple and reasonably scaled approach to separating a NaCaH, into physicochemically different fractions that could be evaluated by a sensory panel. The method of sensory evaluation used in this study, in which NaCaH samples are impregnated into paper-disks, provid...
During processing and digestion, milk proteins are disassembled into peptides with an array of biological functions, including antimicrobial, angiotensin-converting enzyme inhibition, antioxidant, opioid, and immunomodulation. These functions are summarized in numerous reviews, yet information on which peptides have which functions remains scattere...
Background: Peptidomics research has demonstrated that protease activity is higher in breast milk from preterm- delivering mothers than from term-delivering mothers. However, to our knowledge, the effect of the degree of prematurity and postnatal age on proteases and protease inhibitors in human milk remains unknown.
Objective: We aimed to determi...
Milk proteins are a complex and diverse source of biological activities. Beyond their function, intact milk proteins also act as carriers of encrypted functional sequences that, when released as peptides, exert biological functions, including antimicrobial and immunomodulatory activity, which could contribute to the infant's competitive success. Re...
Exclusively breast-fed infants can exhibit clear signs of IgE or non IgE-mediated cow's milk allergy. However, 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. Herein, we aimed at assessing possible CMP-deri...
Proteins are not equally digestible—their proteolytic susceptibility varies by their source and processing method. Incomplete digestion increases colonic microbial protein fermentation (putrefaction), which produces toxic metabolites that can induce inflammation in vitro and have been associated with inflammation in vivo. Individual humans differ i...
Scope:
The microorganisms that make up kefir grains are well known for lactose fermentation, but the extent to which they hydrolyze and consume milk proteins remains poorly understood. Peptidomics technologies were used to examine the proteolytic activity of kefir grains on bovine milk proteins.
Methods and results:
Gel electrophoresis revealed...
Milk contains elements of numerous proteolytic systems (zymogens, active proteases, protease inhibitors and protease activators) produced in part from blood, in part by mammary epithelial cells and in part by immune cell secretion. Researchers have examined milk proteases for decades, as they can cause major defects in milk quality and cheese produ...
Peptidomics is an emerging field branching from proteomics that targets endogenously produced protein fragments. Endogenous peptides are often functional within the body-and can be both beneficial and detrimental. This review covers the use of peptidomics in understanding digestion, and identifying functional peptides and biomarkers. Various techni...
Hundreds of naturally occurring milk peptides are present in term human milk. Preterm milk is produced before complete maturation of the mammary gland, which could change milk synthesis and secretion processes within the mammary gland, leading to differences in protein expression and enzymatic activity, thereby resulting in an altered peptide profi...
Little is known about the digestive process in infants. In particular, the chronological activity of enzymes across the course of digestion in the infant remains largely unknown. To create a temporal picture of how milk proteins are digested, enzyme activity was compared between intact human milk samples from three mothers and the gastric samples f...