scholarly journals Digested formula but not digested fresh human milk causes death of intestinal cells in vitro: implications for necrotizing enterocolitis

2012 ◽  
Vol 72 (6) ◽  
pp. 560-567 ◽  
Author(s):  
Alexander H. Penn ◽  
Angelina E. Altshuler ◽  
James W. Small ◽  
Sharon F. Taylor ◽  
Karen R. Dobkins ◽  
...  
Keyword(s):  
Human Milk ◽  
Necrotizing Enterocolitis ◽  
Intestinal Cells

scholarly journals Human milk glycosaminoglycans inhibit in vitro the adhesion of Escherichia coli and Salmonella fyris to human intestinal cells

2015 ◽  
Vol 79 (4) ◽  
pp. 603-607 ◽  
Author(s):  
Giovanni V. Coppa ◽  
Bruna Facinelli ◽  
Gloria Magi ◽  
Emanuela Marini ◽  
Lucia Zampini ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Human Milk ◽  
Intestinal Cells ◽  
Human Intestinal Cells

scholarly journals The Protective Influence of Chondroitin Sulfate, a Component of Human Milk, on Intestinal Bacterial Invasion and Translocation

2019 ◽  
Vol 35 (3) ◽  
pp. 538-549 ◽  
Author(s):  
Kathryn Y. Burge ◽  
Lindsey Hannah ◽  
Jeffrey V. Eckert ◽  
Aarthi Gunasekaran ◽  
Hala Chaaban
Keyword(s):  
Human Milk ◽  
Bacterial Infection ◽  
Cell Viability ◽  
Chondroitin Sulfate ◽  
Necrotizing Enterocolitis ◽  
Protective Role ◽  
Bacterial Invasion ◽  
Intestinal Inflammatory Disease ◽  
Vitro Model

Background:Human milk is known to be protective against necrotizing enterocolitis, a devastating intestinal inflammatory disease affecting the preterm population. Although the pathogenesis of necrotizing enterocolitis is yet to be solidified, intestinal integrity dysfunction, bacterial invasion and/or translocation, and inflammation may play important roles. Glycosaminoglycans, compounds naturally prevalent in both human milk and the intestine, are thought to be anti-inflammatory and capable of altering bacterial interactions within the gut.Research aim:In this study, we aimed to evaluate the potential of chondroitin sulfate, the most prominent class of glycosaminoglycans in human milk, to protect against bacterial infection in an intestinal in vitro model.Methods:T84 cell monolayers were treated with chondroitin sulfate and cell viability was assessed across a number of doses. Monolayers were then pretreated with chondroitin sulfate and subsequently challenged with E. coli invasion and translocation to evaluate any protective role of the compound against infection. Tight junction barrier function was assessed by transepithelial electrical resistance, and cytokine levels were evaluated.Results:Chondroitin sulfate at any dose up to 750 μg/ml was not associated with any statistically significant decrease in cell viability. Additionally, chondroitin sulfate at 750 μg/ml was associated with a 75% decrease in both bacterial invasion and translocation compared to control.Conclusions:These data suggest chondroitin sulfate may protect against bacterial infection through a reduction in both invasion and translocation, importantly without attendant reduction in cell viability.

scholarly journals Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells

2008 ◽  
Vol 99 (3) ◽  
pp. 462-471 ◽  
Author(s):  
Sabine Kuntz ◽  
Silvia Rudloff ◽  
Clemens Kunz
Keyword(s):  
Human Milk ◽  
Growth Inhibition ◽  
Cell Cycle Progression ◽  
Threshold Concentration ◽  
Intestinal Cells ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Induction Of Differentiation ◽  
Ht 29

Human milk oligosaccharides (HMO) are considered to influence the composition of the gut microflora in breastfed infants. We investigated direct effects of milk HMO fractions or individual oligosaccharides on proliferation, differentiation and apoptosis in transformed human intestinal cells (HT-29 and Caco-2) and non-transformed small intestinal epithelial crypt cells of fetal origin (human intestinal epithelial cells; HIEC). We observed growth inhibition induced by neutral and acidic HMO fractions in HT-29, Caco-2 and HIEC cells in a dose dependent manner. However, the effects varied between cell lines, i.e. HT-29 and Caco-2 cells were more sensitive than HIEC cells. In HT-29, all 16 individual neutral and acidic oligosaccharides except from the two fucosyllactoses had an inhibitory effect on cell growth. Regarding the induction of differentiation in HT-29 and HIEC cells a threshold concentration was observed at 7·5 mg/ml for neutral and acidic HMO fractions. Among individual oligosaccharides, only sialyllactoses induced differentiation in HT-29 and HIEC cells; no effect neither of fractions nor of individual oligosaccharides was found in Caco-2 cells. A strong induction of apoptosis was only detected in HT-29 and HIEC cells for neutral oligosaccharide but not for acidic fractions. HMO were shown to induce growth inhibition in intestinal cells through two different mechanisms, by suppressing cell cycle progression through induction of differentiation and/or by influencing apoptosis. As the development and maturation of digestive and absorptive processes depend on differentiation our experiments show that oligosaccharides are effective at influencing various stages in gastrointestinal development in vitro.

scholarly journals A47 SYNTHETIC HUMAN MILK OLIGOSACCHARIDES PREVENT EXPERIMENTAL NECROTIZING ENTEROCOLITIS VIA DIVERGENT TRANSCRIPTOMIC RESPONSES.

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 272-274
Author(s):  
R Y Wu ◽  
B Li ◽  
R Horne ◽  
A Ghamel ◽  
S Robinson ◽  
...  
Keyword(s):  
Immune Responses ◽  
Human Milk ◽  
Necrotizing Enterocolitis ◽  
Mucosal Injury ◽  
Intestinal Cell ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
In Vivo Models

Abstract Background Breastmilk reduces the risk of necrotizing enterocolitis (NEC) in preterm infants, but the bioactive components mediating this effect are not well understood. Human milk oligosaccharides (HMOs) reduce NEC both in humans and in relevant animal models. However, it is unclear if there are functional differences between individual oligosaccharides. Aims The objective of this study was to compare the intestinal transcriptome responses of individual HMOs using complementary in vitro and in vivo models of NEC. Methods RNA sequencing was performed on Caco-2Bbe1 gut epithelial cells after exposure to commercially-purified 2’-fucosyllactose (2’FL), 3-fucosyllactose, 6’-siallyllactose, lacto-N-tetraose (LNT) or lacto-N-neotetraose for 24hr at 37°C for 24 h (n=3). Signaling pathways were analyzed in murine- and human-derived NEC enteroids by qPCR. To validate these findings, five-day-old mouse pups were orally gavaged formula with or without individual HMOs, followed by NEC induction with hypoxia (5% O2, 95% N2) and lipopolysaccharide (4 mg/kg/day). Coded ileal sections (n=6–7/group) were analyzed for mucosal injury by histology, immune fluorescence, immunohistochemistry, and gene expression via qPCR. Results The HMO transcriptome clustered into divergent functional categories including metabolic process, protein processing and responses to external stimuli. Each synthetic HMO induced a unique transcriptome and exhibited varying effects on the intestinal epithelial functions and biological pathways. This was confirmed in the murine model of NEC, as both LNT and 2FL mitigated NEC injury with comparable recovery of intestinal cell proliferation (Ki67) and expression of stem cells (Lgr5+). Both qPCR and immunofluorescence staining showed differences between 2FL- and LNT-fed pups in host inflammatory and immune responses. Conclusions This study demonstrates that synthetic HMOs ameliorate intestinal injury in experimental NEC. However, the mechanisms by which individual oligosaccharides act on the intestine differ, suggesting that single synthetic HMOs may not fully recapitulate the benefits of pooled HMOs. Future studies will further delineate structure-function relationships of synthetic HMOs on host intestinal innate and adaptive immune responses. Funding Agencies CIHRFerring Canada Medical Student Research grant

scholarly journals Differential impact of Holder and High Temperature Short Time pasteurization on the dynamic in vitro digestion of human milk in a preterm newborn model

2020 ◽  
Vol 328 ◽  
pp. 127126 ◽  
Author(s):  
Stefano Nebbia ◽  
Marzia Giribaldi ◽  
Laura Cavallarin ◽  
Enrico Bertino ◽  
Alessandra Coscia ◽  
...  
Keyword(s):  
High Temperature ◽  
Human Milk ◽  
In Vitro Digestion ◽  
Preterm Newborn ◽  
Differential Impact ◽  
High Temperature Short Time ◽  
Short Time
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