scholarly journals Blends of Human Milk Oligosaccharides Confer Intestinal Epithelial Barrier Protection In Vitro

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3047
Author(s):  
Jane M. Natividad ◽  
Andreas Rytz ◽  
Sonia Keddani ◽  
Gabriela Bergonzelli ◽  
Clara L. Garcia-Rodenas

Breastfeeding is integral in the proper maturation of the intestinal barrier and protection against inflammatory diseases. When human milk (HM) is not available, supplementation with HM bioactives like Human Milk Oligosaccharides (HMOs) may help in providing breastfeeding barrier-protective benefits. An increasing HMO variety is becoming industrially available, enabling approaching the HMO complexity in HM. We aimed at assessing the impact of blends of available HMOs on epithelial barrier function in vitro. The capacity of individual [2′-Fucosyllactose (2′FL), Difucosyllactose, Lacto-N-tetraose, Lacto-N-neotetraose, 3′-Siallylactose and 6′-Siallylactose] or varying combinations of 3, 5 and 6 HMOs to modulate fluorescein-isothiocyanate (FITC)-labelled Dextran 4 KDa (FD4) translocation and/or transepithelial resistance (TEER) was characterized in Caco-2: HT29- methotrexate (MTX) cell line monolayers before and after an inflammatory challenge with TNF-α and IFN-γ. The six HMO blend (HMO6) dose-dependently limited the cytokine-induced FD4 translocation and TEER decrease and increased TEER values before challenge. Similarly, 3 and 5 HMO blends conferred a significant protection against the challenge, with 2′FL, one of the most abundant but most variable oligosaccharides in HM, being a key contributor. Overall, our results suggest differential ability of specific HMOs in modulating the intestinal barrier and support the potential of supplementation with combinations of available HMOs to promote gut health and protect against intestinal inflammatory disorders.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ioannis Kostopoulos ◽  
Janneke Elzinga ◽  
Noora Ottman ◽  
Jay T. Klievink ◽  
Bernadet Blijenberg ◽  
...  

Glycobiology ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 774-786 ◽  
Author(s):  
Sara Porfirio ◽  
Stephanie Archer-Hartmann ◽  
G Brett Moreau ◽  
Girija Ramakrishnan ◽  
Rashidul Haque ◽  
...  

Abstract Human breast milk is an incredibly rich and complex biofluid composed of proteins, lipids and complex carbohydrates, including a diverse repertoire of free human milk oligosaccharides (HMOs). Strikingly, HMOs are not digested by the infant but function as prebiotics for bacterial strains associated with numerous benefits. Considering the broad variety of beneficial effects of HMOs, and the vast number of factors that affect breast milk composition, the analysis of HMO diversity and complexity is of utmost relevance. Using human milk samples from a cohort of Bangladeshi mothers participating in a study on malnutrition and stunting in children, we have characterized breast milk oligosaccharide composition by means of permethylation followed by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS) analysis. This approach identified over 100 different glycoforms and showed a wide diversity of milk composition, with a predominance of fucosylated and sialylated HMOs over nonmodified HMOs. We observed that these samples contain on average 80 HMOs, with the highest permethylated masses detected being >5000 mass units. Here we report an easily implemented method developed for the separation, characterization and relative quantitation of large arrays of HMOs, including higher molecular weight sialylated HMOs. Our ultimate goal is to create a simple, high-throughput method, which can be used for full characterization of sialylated and/or fucosylated HMOs. These results demonstrate how current analytical techniques can be applied to characterize human milk composition, providing new tools to help the scientific community shed new light on the impact of HMOs during infant development.


Pharmacology ◽  
2019 ◽  
Vol 105 (1-2) ◽  
pp. 102-108 ◽  
Author(s):  
Norio Nishii ◽  
Tadayuki Oshima ◽  
Min Li ◽  
Hirotsugu Eda ◽  
Kumiko Nakamura ◽  
...  

Introduction: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. Methods: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1β) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. Results: IFNγ, IL-6, IL-1β, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1β, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. Conclusion: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3052
Author(s):  
Lila S. Nolan ◽  
Jamie M. Rimer ◽  
Misty Good

Preterm infants are a vulnerable population at risk of intestinal dysbiosis. The newborn microbiome is dominated by Bifidobacterium species, though abnormal microbial colonization can occur by exogenous factors such as mode of delivery, formula feeding, and exposure to antibiotics. Therefore, preterm infants are predisposed to sepsis and necrotizing enterocolitis (NEC), a fatal gastrointestinal disorder, due to an impaired intestinal barrier, immature immunity, and a dysbiotic gut microbiome. Properties of human milk serve as protection in the prevention of NEC. Human milk oligosaccharides (HMOs) and the microbiome of breast milk are immunomodulatory components that provide intestinal homeostasis through regulation of the microbiome and protection of the intestinal barrier. Enteral probiotic supplements have been trialed to evaluate their impact on establishing intestinal homeostasis. Here, we review the protective role of HMOs, probiotics, and synbiotic combinations in protecting a vulnerable population from the pathogenic features associated with necrotizing enterocolitis.


2012 ◽  
Vol 108 (10) ◽  
pp. 1839-1846 ◽  
Author(s):  
Evelyn Jantscher-Krenn ◽  
Tineke Lauwaet ◽  
Laura A. Bliss ◽  
Sharon L. Reed ◽  
Frances D. Gillin ◽  
...  

Human milk oligosaccharides (HMO), complex sugars that are highly abundant in breast milk, block viral and bacterial attachment to the infant's intestinal epithelium and lower the risk of infections. We hypothesised that HMO also prevent infections with the protozoan parasiteEntamoeba histolytica,as its major virulence factor is a lectin that facilitates parasite attachment and cytotoxicity and binds galactose (Gal) andN-acetyl-galactosamine. HMO contain Gal, are only minimally digested in the small intestine and reach the colon, the site ofE. histolyticainfection. The objective of the present study was to investigate whether HMO reduceE. histolyticaattachment and cytotoxicity. Ourin vitroresults show that physiological concentrations of isolated, pooled HMO detachE. histolyticaby more than 80 %. In addition, HMO rescueE. histolytica-induced destruction of human intestinal epithelial HT-29 cells in a dose-dependent manner. The cytoprotective effects were structure-specific. Lacto-N-tetraose with its terminal Gal rescued up to 80 % of the HT-29 cells, while HMO with fucose α1–2-linked to the terminal Gal had no effect. Galacto-oligosaccharides (GOS), which also contain terminal Gal and are currently added to infant formula to mimic some of the beneficial effects of HMO, completely abolishedE. histolyticaattachment and cytotoxicity at 8 mg/ml. Although our results need to be confirmedin vivo, they may provide one explanation for why breast-fed infants are at lower risk ofE. histolyticainfections. HMO and GOS are heat tolerant, stable, safe and in the case of GOS, inexpensive, which could make them valuable candidates as alternative preventive and therapeutic anti-amoebic agents.


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