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557 results on '"Newburg, David S."'

105. Human Milk Mucin 1 and Mucin 4 Inhibit Salmonella enterica Serovar Typhimurium Invasion of Human Intestinal Epithelial Cells In Vitro123

Author

Liu, Bo, Yu, Zhuoteng, Chen, Ceng, Kling, David E., and Newburg, David S.

Subjects
Salmonella typhimurium, Nutrition and Disease, Dose-Response Relationship, Drug, Milk, Human, Mucin-4, Mucin-1, Humans, Epithelial Cells, Intestinal Mucosa, Cell Line
Abstract

Many human milk glycans inhibit pathogen binding to host receptors and their consumption by infants is associated with reduced risk of disease. Salmonella infection is more frequent among infants than among the general population, but the incidence is lower in breast-fed babies, suggesting that human milk could contain components that inhibit Salmonella. This study aimed to test whether human milk per se inhibits Salmonella invasion of human intestinal epithelial cells in vitro and, if so, to identify the milk components responsible for inhibition. Salmonella enterica serovar Typhimurium SL1344 (SL1344) invasion of FHs 74 Int and Caco-2 cells were the models of human intestinal epithelium infection. Internalization of fluorescein-5-isothiocyanate-labeled SL1344 into intestinal cells was measured by flow cytometry to quantify infection. Human milk and its fractions inhibited infection; the inhibitory activity localized to the high molecular weight glycans. Mucin 1 and mucin 4 were isolated to homogeneity. At 150 μg/L, a typical concentration in milk, human milk mucin 1 and mucin 4 inhibited SL1344 invasion of both target cell types. These mucins inhibited SL1344 invasion of epithelial cells in a dose-dependent manner. Thus, mucins may prove useful as a basis for developing novel oral prophylactic and therapeutic agents that inhibit infant diseases caused by Salmonella and related pathogens.

Published
2012

117. Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants

Author

Morrow, Ardythe L, primary, Lagomarcino, Anne J, additional, Schibler, Kurt R, additional, Taft, Diana H, additional, Yu, Zhuoteng, additional, Wang, Bo, additional, Altaye, Mekibib, additional, Wagner, Michael, additional, Gevers, Dirk, additional, Ward, Doyle V, additional, Kennedy, Michael A, additional, Huttenhower, Curtis, additional, and Newburg, David S, additional

Published
2013
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123. The Human Milk Oligosaccharide 2'-Fucosyllactose Quenches Campylobacter jejuni--Induced Inflammation in Human Epithelial Cells HEp-2 and HT-29 and in Mouse Intestinal Mucosa.

Author

Zhuo-Teng Yu, Nanthakumar, N. Nanda, and Newburg, David S.

Subjects
CAMPYLOBACTER jejuni, DIARRHEA, MICROBIAL virulence, INTESTINAL mucosa, CARBOHYDRATES, INFLAMMATION
Abstract

Background: Campylobacter jejuni causes diarrhea worldwide; young children are most susceptible. Binding of virulent C. jejuni to the intestinal mucosa is inhibited ex vivo by α1,2-fucosylated carbohydrate moieties, including human milk oligosaccharides (HMOSs). Objective: The simplest α1,2-fucosylated HMOS structure, 2'-fucosyllactose (2'-FL), can be predominant at ≤5 g/L milk. Although 2'-FL inhibits C. jejuni binding ex vivo and in vivo, the effects of 2'FL on the cell invasion central to C. jejuni pathogenesis have not been tested. Clinical isolates of C. jejuni infect humans, birds, and ferrets, limiting studies on its mammalian pathobiology. Methods: Human epithelial cells HEp-2 and HT-29 infected with the virulent C. jejuni strain 81-176 human isolate were treated with 5 g 2'-FL/L, and the degree of infection and inflammatory response was measured. Four-week-old male wild-type C57BL/6 mice were fed antibiotics to reduce their intestinal microbiota and were inoculated with C. jejuni strain 81-176. The sensitivity of the resulting acute transient enteric infection and immune response to inhibition by 2'-FL ingestion was tested. Results: In HEp-2 and HT-29 cells, 2'-FL attenuated 80% of C. jejuni invasion (P < 0.05) and suppressed the release of mucosal proinflammatory signals of interleukin (IL) 8 by 60-70%, IL-1β by 80-90%, and the neutrophil chemoattractant macrophage inflammatory protein 2 (MIP-2) by 50% (P < 0.05). Ingestion of 2'-FL by mice reduced C. jejuni colonization by 80%, weight loss by 5%, histologic features of intestinal inflammation by 50-70%, and induction of inflammatory signaling molecules of the acute-phase mucosal immune response by 50-60% (P < 0.05). This acute model did not induce IL-17 (adaptive T cell response), a chronic response. Conclusions: In human cells in vitro (HEp-2, HT-29) and in a mouse infection model that recapitulated key pathologic features of C. jejuni clinical disease, 2'-FL inhibited pathogenesis and its sequelae. These data strongly support the hypothesis that 2'-FL represents a new class of oral agent for prevention, and potentially for treatment, of specific enteric infectious diseases. [ABSTRACT FROM AUTHOR]

Published
2016
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124. The human milk oligosaccharide 20-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation.

Author

YingYing He, ShuBai Liu, Kling, David E., Leone, Serena, Lawlor, Nathan T., Yi Huang, Feinberg, Samuel B., Hill, David R., and Newburg, David S.

Subjects
INTESTINAL infections, BREAST milk, OLIGOSACCHARIDES, LACTOSE, CD14 antigen, ENTEROCYTES, PHYSIOLOGICAL effects of lipopolysaccharides, FUCOSYLATION, THERAPEUTICS
Abstract

Background: A major cause of enteric infection, Gram-negative pathogenic bacteria activate mucosal inflammation through lipopolysaccharide (LPS) binding to intestinal toll-like receptor 4 (TLR4). Breast feeding lowers risk of disease, and human milk modulates inflammation. Objective: This study tested whether human milk oligosaccharides (HMOSs) influence pathogenic Escherichia coli-induced interleukin (IL)-8 release by intestinal epithelial cells (IECs), identified specific proinflammatory signalling molecules modulated by HMOSs, specified the active HMOS and determined its mechanism of action. Methods: Models of inflammation were IECs invaded by type 1 pili enterotoxigenic E. coli (ETEC) in vitro: T84 modelled mature, and H4 modelled immature IECs. LPSinduced signalling molecules co-varying with IL-8 release in the presence or absence of HMOSs were identified. Knockdown and overexpression verified signalling mediators. The oligosaccharide responsible for altered signalling was identified. Results: HMOSs attenuated LPS-dependent induction of IL-8 caused by ETEC, uropathogenic E. coli, and adherent-invasive E. coli (AIEC) infection, and suppressed CD14 transcription and translation. CD14 knockdown recapitulated HMOS-induced attenuation. Overexpression of CD14 increased the inflammatory response to ETEC and sensitivity to inhibition by HMOSs. 20-fucosyllactose (20-FL), at milk concentrations, displayed equivalent ability as total HMOSs to suppress CD14 expression, and protected AIEC-infected mice. Conclusions: HMOSs and 20-FL directly inhibit LPSmediated inflammation during ETEC invasion of T84 and H4 IECs through attenuation of CD14 induction. CD14 expression mediates LPS-TLR4 stimulation of portions of the 'macrophage migration inhibitory factors' inflammatory pathway via suppressors of cytokine signalling 2/signal transducer and activator of transcription 3/NF-B. HMOS direct inhibition of inflammation supports its functioning as an innate immune system whereby the mother protects her vulnerable neonate through her milk. 20-FL, a principal HMOS, quenches inflammatory signalling. [ABSTRACT FROM AUTHOR]

Published
2016
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134. Part 2-Prebiotics

Author

Dubert-Ferrandon, Alix, primary, Newburg, David S., additional, and Walker, W. Allan, additional

Published
2009
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135. Part 1-Prebiotics

Author

Dubert-Ferrandon, Alix, primary, Newburg, David S., additional, and Walker, W. Allan, additional

Published
2008
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139. Neonatal Gut Microbiota and Human Milk Glycans Cooperate to Attenuate Infection and Inflammation.

Author

NEWBURG, DAVID S. and YINGYING HE

Subjects
*INFECTION prevention, *GUT microbiome, *BREAST milk, *INFLAMMATORY mediators, *POLYSACCHARIDES, *PREBIOTICS, *CHILDREN
Abstract

Glycans of the intestinal mucosa and oligosaccharides of human milk influence the early colonization of the infant gut and establishment of mucosal homeostasis, and differences in colonization of the gut influence the ontogeny of glycans on the surface of the intestinal mucosa, proinflammatory signaling, homeostasis, and resilience to insult. This interkingdom reciprocal interaction is typical of a mutualistic symbiotic relationship. The period in which the infant gut most needs protection from hypersensitive inflammation overlaps with the recommended period of exclusive nursing; electively substituting artificial formula that lacks human milk protective glycans seems ill advised, especially for premature infants. [ABSTRACT FROM AUTHOR]

Published
2015
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143. Noroviruses Bind to Human ABO, Lewis, and Secretor Histo–Blood Group Antigens: Identification of 4 Distinct Strain‐Specific Patterns

Author

Huang, Pengwei, primary, Farkas, Tibor, additional, Marionneau, Séverine, additional, Zhong, Weiming, additional, Ruvoën‐Clouet, Nathalie, additional, Morrow, Ardythe L., additional, Altaye, Mekibib, additional, Pickering, Larry K., additional, Newburg, David S., additional, LePendu, Jacques, additional, and Jiang, Xi, additional

Published
2003
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150. Human Milk Components Modulate Toll-Like Receptor–Mediated Inflammation

Author

He, YingYing, Lawlor, Nathan T, and Newburg, David S

Abstract

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2′-fucosyllactose attenuate TLR4 signaling; 3′-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling.

Published
2016
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