Dataset Information

Immunomodulatory and Prebiotic Effects of 2'-Fucosyllactose in Suckling Rats.

ABSTRACT: Human milk oligosaccharides are unconjugated complex glycans present in high concentration in human milk that serve as pre-biotics and immunomodulators. They are not primarily absorbed or metabolized by the infant and reach the lower part of the intestinal tract unaltered. One of the main oligosaccharides found in human milk is 2'-fucosyllactose (2'-FL). This study aimed to investigate the effects of daily oral administration of 2'-FL in healthy suckling rats. From days 2 to 16 of life, rats were daily given the oligosaccharide (2'-FL) or vehicle (REF), weighed and their stool characteristics were assessed. On days 8 and 16 of life the morphometry, intestinal architecture, and cytokine release, mesenteric lymph nodes cell composition, plasma immunoglobulin concentrations, fecal microbiota composition, cecal short-chain fatty acids content, and the urinary metabolic profile were assessed. Animals given 2'-FL showed higher plasma IgG and IgA and more T cell subsets in the mesenteric lymph nodes on day 16. Moreover, at intestinal level, villus heights, and areas were increased on day 8. Cecal samples displayed a higher Lactobacillus proportion and a different urinary metabolic profile was observed on day 8, and a higher proportion of butyrate on day 16. In conclusion, supplementation of 2'-FL in early life has a pre-biotic and intestinal trophic effect and promotes maturation of the immune system.

SUBMITTER: Azagra-Boronat I

PROVIDER: S-EPMC6685134 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Immunomodulatory and Prebiotic Effects of 2'-Fucosyllactose in Suckling Rats.

Azagra-Boronat Ignasi I Massot-Cladera Malén M Mayneris-Perxachs Jordi J Knipping Karen K Van't Land Belinda B Tims Sebastian S Stahl Bernd B Garssen Johan J Franch Àngels À Castell Margarida M Rodríguez-Lagunas M José MJ Pérez-Cano Francisco J FJ

Frontiers in immunology 20190731

Human milk oligosaccharides are unconjugated complex glycans present in high concentration in human milk that serve as pre-biotics and immunomodulators. They are not primarily absorbed or metabolized by the infant and reach the lower part of the intestinal tract unaltered. One of the main oligosaccharides found in human milk is 2'-fucosyllactose (2'-FL). This study aimed to investigate the effects of daily oral administration of 2'-FL in healthy suckling rats. From days 2 to 16 of life, rats wer ...[more]

PMID: 31417553

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Project description:IntroductionEarly life exposure to non-digestible oligosaccharides (NDO) or microbial components is known to affect immune development. NDO in combination with a TLR9 agonist mimicking bacterial triggers (CpG) promoted the secretion of galectins through unknown pathways. We aimed to study the contribution of exosomes in epithelial galectin secretion and subsequent immunoregulation upon exposure to a mixture of NDO by inhibiting exosome biogenesis.MethodsHuman intestinal epithelial cells (IEC) (FHs 74 Int or HT-29) were apically exposed to 2'-fucosyllactose (2'FL) and short-chain galacto- and long-chain fructo-oligosaccharides (GF), alone or with CpG. Basolaterally, non-activated or αCD3/CD28-activated peripheral blood mononuclear cells (PBMC) were added. After 24 h incubation, IEC were washed and incubated in fresh medium to analyze epithelial-derived galectin secretion. Additionally, before exposure to NDO and CpG, IEC were exposed to GW4869 to inhibit exosome biogenesis. After 24 h of incubation, IEC were washed and incubated for additional 24 h in the presence of GW4869, after which epithelial-derived galectin secretion was studied. Also, epithelial-derived exosomes were isolated to study the presence of galectins within the exosomes.ResultsCompared to CpG alone, exposure to 2'FL/GF mixture and CpG, significantly enhanced Th1-type IFNγ, and regulatory IEC-derived galectin-9 secretion in the HT-29/PBMC model. Similarly, in the FHs 74 Int/PBMC co-culture, 2'FL/GF induced immunomodulatory effects in the absence of CpG. Interestingly, galectin-9 and -4 were present in CD63-expressing exosomes isolated from HT-29 supernatants after IEC/PBMC co-culture. Exposure to GW4869 suppressed 2'FL/GF and CpG induced epithelial-derived galectin-9 secretion, which subsequently prevented the rise in IL-10 and reduction in IL-13 secretion observed in the HT-29/PBMC co-culture model upon exposure to 2'FL/GF and CpG.DiscussionExposure to 2'FL/GF and CpG or 2'FL/GF promoted Th1-type regulatory effects in HT-29/PBMC or FHs 74 Int/PBMC co-culture respectively, while Th2-type IL-13 was reduced in association with increased galectin-9 release. Galectin-9 and -4 were present in exosomes from HT-29 and the inhibition of exosome biogenesis inhibited epithelial-derived galectin secretion. This, also affected immunomodulatory effects in IEC/PBMC co-culture suggesting a key role of galectin expressing IEC-derived exosomes in the mucosal immune regulation induced by NDO.

Project description:Objectives: Colistin has been identified in a Caenorhabditis elegans chemical screening as an immunostimulatory agent that activates the conserved p38/PMK-1 pathway and provides protection against pathogens. Here we aimed to extend those findings to a mammalian model and evaluate the immunomodulatory effects of colistin on rat macrophages. Methods: Macrophages were isolated from Sprague-Dawley (SD) rat. The effects of colistin on the cytokine secretion, phagocytic activity and protein expression were determined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, and Western blotting analysis, respectively. The relative microRNA expression was determined by microarray, and Kyoto Encylopedia of Genes and Genomes (KEGG) was used to identify potential signaling pathways. Results: Our data showed that 5, 10, and 20 µg/ml colistin significantly increased the secretion of TNF-α, while 20 and 5 µg/ml colistin significantly increased the levels of IL-1β and IL-6, respectively. Flow cytometry results showed that the relative mean fluorescence intensity and percentage of phagocytosis in colistin treatment groups were significantly higher compared with the control group, while the increased phagocytosis phenomenon can be blocked by p38 inhibitor. The phagocytic ability of macrophages against Staphylococcus aureus was significantly increased after colistin treatment. Microarray and KEGG pathway analyses revealed that mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), chemokine, and B cell receptor were the main pathways involved in the colistin stimulation process. Western blotting analysis demonstrated that the phosphorylated p38 protein level of colistin treatment groups was increased in a dose dependent manner. Conclusions: Present study is the first to demonstrate that colistin had immunomodulatory effects on macrophages in mammals, and the p38/MAPK pathway was involved in such colistin-induced immunomodulatory effect.

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Immunomodulatory and Prebiotic Effects of 2'-Fucosyllactose in Suckling Rats.

Publications

Immunomodulatory and Prebiotic Effects of 2'-Fucosyllactose in Suckling Rats.

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