Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of <scp>TLR</scp>4‐<scp>NF</scp>κ<scp>B</scp>

Ortega‐González, Mercedes; Ocón, Borja; Romero‐Calvo, Isabel; Anzola, Andrea; Guadix, Emilia M.; Zarzuelo, Antonio; Suárez, Marı́a Dolores; Martínez‐Augustin, Olga

doi:10.1002/mnfr.201300296

Cited by 100 publications

(94 citation statements)

References 33 publications

(43 reference statements)

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“…Induced CCL2 secretion by non-digestible saccharides was suppressed in colonic explants of TLR4 knockout mice as well as TLR4 or myeloid differentiation primary response gene 88 knockdowns in IEC-18 cells (18). Additionally, the inhibitors of TLR4 signaling-related molecules such as ERK1/2, JNK, p38, MAPK, and NF-κB suppressed CCL2 production in IEC-18 cells (18), suggesting that the activation of the TLR4 signaling pathway is involved in the response induced by nondigestible saccharides.…”

Section: Discussionmentioning

confidence: 96%

Megalo-type α-1,6-glucosaccharides induce production of tumor necrosis factor α in primary macrophages via toll-like receptor 4 signaling

Joe¹,

Andoh²,

Shinoki³

et al. 2016

Biomed. Res.

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The term "megalo-saccharide" is used for saccharides with ten or more saccharide units, whereas the term "oligo-saccharide" is used for saccharides containing fewer than ten monosaccharide units. Megalo-type α-1,6-glucosaccharide (M-IM) is a non-digestible saccharide and not utilized by intestinal bacteria, suggesting that ingested M-IM may encounter ileum Peyer's patches that contains immune cells such as macrophages. Macrophages are responsible for antigen incorporation and presentation during the initial step of immune responses. We investigated whether M-IMs modulate macrophage functions such as cytokine production, nitric oxide production, cell viability, and phagocytosis. Primary macrophages collected from the rats were cultured with the existence of M-IM or lipopolysaccharides (LPS). M-IM and LPS induced the production of tumor necrosis factor α (TNFα), interleukin 6 (IL6), and nitric oxide in the primary macrophages. The gene expression profile of inflammatory factors including TNFα, IL6, and ILlβ in M-IM-stimulated cells was similar to that of LPS-stimulated cells. The M-IM did not affect phagocytosis in the primary macrophages. The M-IM-induced TNFα production was suppressed in the cells treated with a tolllike receptor 4 (TLR4) inhibitor called TAK-242. In conclusion, the M-IM modulates cytokine expression via TLR4 signaling and may play a role in the modulation of immune responses.

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Section: Discussionmentioning

confidence: 96%

Megalo-type α-1,6-glucosaccharides induce production of tumor necrosis factor α in primary macrophages via toll-like receptor 4 signaling

Joe¹,

Andoh²,

Shinoki³

et al. 2016

Biomed. Res.

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“…Moreover, GOS seem to exert direct, microbiota-independent effects on the immune system by interacting with epithelial and immune cells, as indicated by in vitro experiments [3,6,7,46]. Although direct interaction with TLR4 has been hypothesized [46], the direct effect of GOS on tight junction assembly in Caco-2 cells [6] indicates the involvement of other mechanisms as well, since Caco-2 cells do not express TLR4.…”

Section: Discussionmentioning

confidence: 99%

“…Although direct interaction with TLR4 has been hypothesized [46], the direct effect of GOS on tight junction assembly in Caco-2 cells [6] indicates the involvement of other mechanisms as well, since Caco-2 cells do not express TLR4. Furthermore, different galectins have distinct binding specificities for binding oligosaccharides [47].…”

Section: Discussionmentioning

confidence: 99%

Inflammation-Induced Expression of the Alarmin Interleukin 33 Can Be Suppressed by Galacto-Oligosaccharides

Verheijden

Akbari²,

Willemsen³

et al. 2015

Int Arch Allergy Immunol

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Background: The alarmin interleukin 33 (IL-33) and its receptor ST2 play an important role in mucosal barrier tissues, and seem to be crucial for Th2-cell mediated host defense. Galacto-oligosaccharides (GOS), used in infant formulas, exhibit gut and immune modulatory effects. To enhance our understanding of the immunomodulatory capacity of GOS, this study investigated the impact of dietary GOS intervention on IL-33 and ST2 expression related to intestinal barrier dysfunction and asthma. Methods: B6C3F₁ and BALB/c mice were fed a control diet with or without 1% GOS. To simulate intestinal barrier dysfunction, B6C3F₁ mice received a gavage with the mycotoxin deoxynivalenol (DON). To mimic asthma-like inflammatory airway responses, BALB/c mice were sensitized on day 0 and challenged on days 7-11 with house-dust mite (HDM) allergen. Samples from the intestines and lungs were collected for IL-33 and ST2 analysis by qRT-PCR, immunoblotting and immunohistochemistry. Results: Dietary GOS counteracted the DON-induced IL-33 mRNA expression and changed the IL-33 distribution pattern in the mouse small intestine. The IL-33 mRNA expression was positively correlated to the intestinal permeability. A strong positive correlation was also observed between IL-33 mRNA expression in the lung and the number of bronchoalveolar fluid cells. Reduced levels of IL-33 protein, altered IL-33 distribution and reduced ST2 mRNA expression were observed in the lungs of HDM-allergic mice after GOS intervention. Conclusions: Dietary GOS mitigated IL-33 at the mucosal surfaces in a murine model for intestinal barrier dysfunction and HDM-induced asthma. This promising effect may open up new avenues to use GOS not only as a prebiotic in infant nutrition, but also as a functional ingredient that targets inflammatory processes and allergies associated with IL-33 expression.

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“…In addition to modulating the composition of the gut microbiome, current studies indicate that these prebiotic oligosaccharides can inhibit enteropathogen adhesion to host surfaces (87) and directly influence epithelial cell anti-inflammatory cytokine gene expression (79). Prebiotics can also directly promote intestinal cell barrier integrity by activating TLR-2 (88), enhancing tight junction claudin-3 assembly (89), and directly altering epithelial cytokine expression (90). These effects were thought to be due to the activation of pattern recognition receptors (91); however, evidence from animal studies is limited and further studies in this area are needed.…”

Section: Management Strategiesmentioning

confidence: 99%

Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis

Johnson‐Henry

Abrahamsson

et al. 2016

Advances in Nutrition

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Necrotizing enterocolitis (NEC) is a devastating intestinal disease in preterm infants characterized by barrier disruption, intestinal microbial dysbiosis, and persistent inflammation of the colon, which results in high mortality rates. Current strategies used to manage this disease are not sufficient, although the use of human breast milk reduces the risk of NEC. Mother's milk is regarded as a fundamental nutritional source for neonates, but pasteurization of donor breast milk affects the composition of bioactive compounds. Current research is evaluating the benefits and potential pitfalls of adding probiotics and prebiotics to pasteurized milk so as to improve the functionality of the milk and thereby reduce the burden of illness caused by NEC. Probiotics (live micro-organisms that confer health to the host) and prebiotics (nondigestible oligosaccharides that stimulate the growth of healthy bacteria) are functional foods known to mediate immune responses and modulate microbial populations in the gut. Clinical research shows strain-and compoundspecific responses when probiotics or prebiotics are administered in conjunction with donor breast milk for the prevention of NEC. Despite ongoing controversy surrounding optimal treatment strategies, randomized controlled studies are now investigating the use of synbiotics to reduce the incidence and severity of NEC. Synbiotics, a combination of probiotics and prebiotics, have been proposed to enhance beneficial health effects in the intestinal tract more than either agent administered alone. This review considers the implications of using probiotic-, prebiotic-, and synbioticsupplemented breast milk as a strategy to prevent NEC and issues that could be encountered with the preparations. Adv Nutr 2016;7:928-37.

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Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR4‐NFκB

Abstract: We conclude that prebiotics are TLR4 ligands in intestinal epithelial cells and that this may be a relevant mechanism for their in vivo effects.

Cited by 100 publications

References 33 publications

<b>Megalo-type α-1,6-glucosaccharides induce production of tumor necrosis factor α in primary macrophages via toll-like receptor 4 </b><b>signaling </b>

<b>Megalo-type α-1,6-glucosaccharides induce production of tumor necrosis factor α in primary macrophages via toll-like receptor 4 </b><b>signaling </b>

Inflammation-Induced Expression of the Alarmin Interleukin 33 Can Be Suppressed by Galacto-Oligosaccharides

Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis

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