Human Milk Oligosaccharides and Synthetic Galactosyloligosaccharides Contain 3′-, 4-, and 6′-Galactosyllactose and Attenuate Inflammation in Human T84, NCM-460, and H4 Cells and Intestinal Tissue Ex Vivo

Newburg, David S.; Ko, Jae Sung; Leone, Serena; Nanthakumar, N. Nanda

doi:10.3945/jn.115.220749

Cited by 83 publications

(82 citation statements)

References 45 publications

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“…. In contrast, arabinoxylan and mixed-linked β-glucans did not affect the basal production of IL-8 by Caco-2 and HT-29 cells (Samuelsen et al, 2011), which is in agreement with the unaltered basal expression of proinflammatory mediators in human colonic epithelial cells incubated with pooled HMOs (Newburg, Ko, Leone, & Nanthakumar, 2016).…”

Section: Dietary Fibre Interaction With the Epidermal Growth Factorsupporting

confidence: 82%

Microbiota‐dependent and ‐independent effects of dietary fibre on human health

Cai

Folkerts

et al. 2019

British J Pharmacology

102

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Dietary fibre, such as indigestible oligosaccharides and polysaccharides, occurs in many foods and has gained considerable importance related to its beneficial effects on host health and specific diseases. Dietary fibre is neither digested nor absorbed in the small intestine and modulates the composition of the gut microbiota. New evidence indicates that dietary fibre also interacts directly with the epithelium and immune cells throughout the gastrointestinal tract by microbiota‐independent effects. This review focuses on how dietary fibre improves human health and the reported health benefits that are connected to molecular pathways, in (a) a microbiota‐independent manner, via interaction with specific surface receptors on epithelial and immune cells regulating intestinal barrier and immune function, and (b) a microbiota‐dependent manner via maintaining intestinal homeostasis by promoting beneficial microbes, including Bifidobacteria and Lactobacilli, limiting the growth, adhesion, and cytotoxicity of pathogenic microbes, as well as stimulating fibre‐derived microbial short‐chain fatty acid production. Linked Articles This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc

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Section: Dietary Fibre Interaction With the Epidermal Growth Factorsupporting

confidence: 82%

Microbiota‐dependent and ‐independent effects of dietary fibre on human health

Cai

Folkerts

et al. 2019

British J Pharmacology

102

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“…Previous studies have indicated that specific oligosaccharides can modulate multiple functions of intestinal epithelial cells, in vitro , in vivo and ex vivo (He et al., ; Holscher, Davis, & Tappenden, ; Kuntz et al., ; Kuntz, Kunz, & Rudloff, ; Newburg et al., ; Ortega‐Gonzalez et al., ; Zenhom et al., ). 3’‐sialyllactose and fructooligosaccharides were demonstrated to inhibit baseline chemokine expression and release from the Caco‐2 human intestinal cell line (Zenhom et al., ), while pooled HMOs and synthetic galactosyloligosaccharides were demonstrated to inhibit TNFα and salmonella induced chemokine release from human intestinal cell lines and immature intestinal tissue (Newburg et al., ), but did not appear to alter baseline levels. Similarly, 2’FL was demonstrated to inhibit E.coli induced IL‐8 release through a mechanism involving down‐regulation of the LPS receptor complex component CD14 (He et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…Most of these beneficial effects depend on the specific structures of HMOs, with clear distinctions between nonsialylated (neutral) and sialylated (acidic) oligosaccharides (van Hoffen et al., ). Indeed, previous studies have identified that synthetic, plant based and milk derived oligosaccharides can modulate multiple signaling pathways in intestinal epithelial cells, where they have been demonstrated to both inhibit (He et al., ; Newburg, Ko, Leone, & Nanthakumar, ; Zenhom et al., ) and enhance (Ortega‐Gonzalez et al., ) responses to inflammatory signals associated with infection. Such studies suggest the possibility of multiple HMOs having distinct functions, including modulation of various inflammatory signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Human Milk Oligosaccharides Attenuate Antigen–Antibody Complex Induced Chemokine Release from Human Intestinal Epithelial Cell Lines

Zehra

Khambati

Vierhout

et al. 2018

Journal of Food Science

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This study provides evidence for direct effects of HMOs in addition to their prebiotic role and demonstrates, for the first time, modulation of Ag-IgE complex activation of human epithelial cells that may have important implications for food-allergy. The study also reinforces the concept that structurally different oligosaccharides have distinct biological activities. In determining the composition of infant formula, addition of oligosaccharides with specific structures may provide direct modulation of immune responses and potentially attenuate symptoms or development of food allergy.

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“…One approach to prevention is through changing the infant diet, as NEC risk is known to be significantly lower in breastfed infants due to protection provided by various breastmilk components . One such component is human milk oligosaccharides (HMOs), a highly abundant group of indigestible oligosaccharides (5–15 g L –1 ) that: i) stimulate growth of gut commensals, ii) prevent adhesion of enteropathogens, and iii) modulate host immunity . In humans, reduced HMO exposure during the first month of life is linked to the development of NEC .…”

Section: Introductionmentioning

confidence: 99%

Human Milk Oligosaccharides Increase Mucin Expression in Experimental Necrotizing Enterocolitis

Koike

et al. 2018

Molecular Nutrition Food Res

119

117

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Scope Necrotizing enterocolitis (NEC) is a leading cause of morbidity and death in preterm infants, occurring more often in formula‐fed than breastfed infants. Studies in both rats and humans show that human milk oligosaccharides (HMOs) lower the incidence of NEC, but the mechanism underlying such protection is currently unclear. Methods and Results By extracting HMOs from pooled human breastmilk, the impact of HMOs on the intestinal mucin levels in a murine model of NEC are investigated. To confirm the results, the findings are validated by exposing human intestinal epithelial cells and intestinal organoids to HMOs and evaluated for mucin expression. HMO‐gavage to pups increases Muc2 levels and decreases intestinal permeability to macromolecular dextran. HMO‐treated cells have increased Muc2 expression, decreased bacterial attachment and dextran permeability during challenge by enteric pathogens. To identify the mediators involved in HMO induction of mucins, it is demonstrated that HMOs directly induce the expression of chaperone proteins including protein disulfide isomerase (PDI). Suppression of PDI activity removes the protective effects of HMOs on barrier function in vitro as well as NEC protection in vivo. Conclusions Taken together, the results provide insights to the possible mechanisms by which HMOs protect the neonatal intestine through upregulation of mucins.

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Human Milk Oligosaccharides and Synthetic Galactosyloligosaccharides Contain 3′-, 4-, and 6′-Galactosyllactose and Attenuate Inflammation in Human T84, NCM-460, and H4 Cells and Intestinal Tissue Ex Vivo

Cited by 83 publications

References 45 publications

Microbiota‐dependent and ‐independent effects of dietary fibre on human health

Microbiota‐dependent and ‐independent effects of dietary fibre on human health

Human Milk Oligosaccharides Attenuate Antigen–Antibody Complex Induced Chemokine Release from Human Intestinal Epithelial Cell Lines

Human Milk Oligosaccharides Increase Mucin Expression in Experimental Necrotizing Enterocolitis

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