Dietary Xylooligosaccharide Downregulates IFN-γ and the Low-Grade Inflammatory Cytokine IL-1β Systemically in Mice

Hansen, Camilla Hartmann Friis; Frøkiær, Hanne; Christensen, Annette G.; Bergström, Anders; Licht, Tine Rask; Hansen, Axel Kornerup; Metzdorff, Stine Broeng

doi:10.3945/jn.112.172361

Cited by 81 publications

(80 citation statements)

References 39 publications

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“…Increase of serum IL-2, IL-4 and INF-γ in rats exposed to high altitude hypoxia environment was observed in the study. INF-γ is a cytokine that is critical for innate and adaptive immunity against viral and bacterial infections [28,29]. However, administration of vitamin E inhibited the increase of IL-2, IL-4 and INF-γ.…”

Section: Discussionmentioning

confidence: 99%

Effect of Vitamin E Supplementation on Intestinal Barrier Function in Rats Exposed to High Altitude Hypoxia Environment

Sun

Qiao

et al. 2014

Korean J Physiol Pharmacol

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The study was conducted to investigate the role of vitamin E in the high altitude hypoxia-induced damage to the intestinal barrier in rats. Sprague-Dawley rats were divided into control (Control), high altitude hypoxia (HH), and high altitude hypoxia+vitamin E (250 mg/kg BW*d) (HV) groups. After the third day, the HH and HV groups were placed in a hypobaric chamber at a stimulated elevation of 7000 m for 5 days. The rats in the HV group were given vitamin E by gavage daily for 8 days. The other rats were given equal volume saline. The results showed that high altitude hypoxia caused the enlargement of heart, liver, lung and kidney, and intestinal villi damage. Supplementation with vitamin E significantly alleviated hypoxia-caused damage to the main organs including intestine, increased the serum superoxide dismutase (SOD) (p< 0.05), diamino oxidase (DAO) (p< 0.01) levels, and decreased the serum levels of interleukin-2 (IL-2) (p< 0.01), interleukin-4 (IL-4) (p<0.001), interferon-gamma (IFN-γ) (p<0.01) and malondialdehyde (MDA) (p<0.001), and decreased the serum erythropoietin (EPO) activity (p<0.05). Administration of vitamin E significantly increased the S-IgA (p<0.001) in ileum and significantly improved the expression levels of occludin and IκBα, and decreased the expression levels of hypoxia-inducible factor 1 alpha and 2 alpha (HIF-1α and HIF-2α), Toll-like receptors (TLR4), P-IκBα and nuclear factor-κB p65(NF-κB P65) in ileum compared to the HH group. This study suggested that vitamin E protectis from intestinal injury caused by high altitude hypoxia environment. These effects may be related to the HIF and TLR4/NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Effect of Vitamin E Supplementation on Intestinal Barrier Function in Rats Exposed to High Altitude Hypoxia Environment

Sun

Qiao

et al. 2014

Korean J Physiol Pharmacol

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“…Homogenization, RNA isolation with MagMAX-96 RNA Isolation Kit (Ambion), and cDNA synthesis using the High-Capacity cDNA Reverse Transcriptase Kit (Applied Biosystems, Foster City, CA) were performed as described previously (25). An inventoried TaqMan Mouse Immune Array (Appled Biosystems) containing 90 TaqMan gene expression assays of immune-related genes was used to investigate ileal samples isolated at weaning, which were analyzed as described previously (26).…”

Section: Quantitative Pcrmentioning

confidence: 99%

“…An inventoried TaqMan Mouse Immune Array (Appled Biosystems) containing 90 TaqMan gene expression assays of immune-related genes was used to investigate ileal samples isolated at weaning, which were analyzed as described previously (26). Actinb, Ocln, Tjp1, Cldn8, Cldn15, Muc1, and Muc2 TaqMan gene expression assays (Applied Biosystems) were used for quantitative PCR (qPCR) analyses on ileum and colon cDNA isolated at 4 weeks of age, and the data were analyzed as described previously (25).…”

Section: Quantitative Pcrmentioning

confidence: 99%

A Maternal Gluten-Free Diet Reduces Inflammation and Diabetes Incidence in the Offspring of NOD Mice

et al. 2014

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Early-life interventions in the intestinal environment have previously been shown to influence diabetes incidence. We therefore hypothesized that a gluten-free (GF) diet, known to decrease the incidence of type 1 diabetes, would protect against the development of diabetes when fed only during the pregnancy and lactation period. Pregnant nonobese diabetic (NOD) mice were fed a GF or standard diet until all pups were weaned to a standard diet. The early-life GF environment dramatically decreased the incidence of diabetes and insulitis. Gut microbiota analysis by 16S rRNA gene sequencing revealed a pronounced difference between both mothers and their offspring on different diets, characterized by increased numbers of Akkermansia, Proteobacteria, and TM7 in the GF diet group. In addition, pancreatic forkhead box P3 regulatory T cells were increased in GF-fed offspring, as were M2 macrophage gene markers and tight junction-related genes in the gut, while intestinal gene expression of proinflammatory cytokines was reduced. An increased proportion of T cells in the pancreas expressing the mucosal integrin a4b7 suggests that the mechanism involves increased trafficking of gut-primed immune cells to the pancreas. In conclusion, a GF diet during fetal and early postnatal life reduces the incidence of diabetes. The mechanism may involve changes in gut microbiota and shifts to a less proinflammatory immunological milieu in the gut and pancreas.Gluten has previously been shown to affect the development of type 1 diabetes (T1D) in animal models. A gluten-free (GF) diet decreased the incidence of diabetes from 64% to 15% when nonobese diabetic (NOD) mice were fed a GF diet after weaning (1), and eating a GF diet decreased the incidence of diabetes to just 6% in the offspring in two generations, which indicates that the interplay between gut antigens and immune pathways leading to diabetes is particularly important in the preweaning period when insulitis starts to progress (2).Accumulating evidence suggests that gut immune reactivity is skewed in human and murine diabetic patients. Studies in young human patients with T1D have demonstrated increased numbers of interferon-g (IFN-g)-producing, interleukin (IL)-1a-producing, and IL-4-producing cells in the small intestinal lamina propria, reflecting T1D preceded by intestinal immune activation (3). Similarly in NOD mice, a diabetes-promoting diet induced proinflammatory cytokines IFN-g and tumor necrosis factor-a in the small intestinal lamina propria (4), and an antidiabetogenic diet decreased the high numbers of CD11b + CD11c+ dendritic cells (DCs) found in the colon lamina propria (5). Under germ-free conditions, reduced expression of forkhead box P3 (FoxP3) in the ileum, colon, and the draining lymph node was associated with accelerated development of insulitis in NOD mice (6), and, likewise in humans, Badami et al. (7) found that jejunal biopsy samples from T1D patients showed reduced frequency of CD42 regulatory T cells (Tregs). The link between the gut and pancreas has also...

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“…Homogenization, RNA isolation with MagMAX-96 RNA Isolation Kit (Ambion), and cDNA synthesis using High-Capacity cDNA Reverse Transcriptase Kit (Applied Biosystems, Foster City, CA) were performed as described previously (38). Tgfb, Il10, Tnfa, Ifng, Il1b TaqMan gene ex-pression assays (Applied Biosystems) were used for quantitative PCR analysis, and data were analyzed as described previously (38). In brief, fold changes in gene expression were calculated by the comparative cycle threshold (C T ) method.…”

Section: Cytokine Expression By Quantitative Pcrmentioning

confidence: 99%

Mode of Delivery Shapes Gut Colonization Pattern and Modulates Regulatory Immunity in Mice

Hansen

Andersen

Krych

et al. 2014

The Journal of Immunology

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Delivery mode has been associated with long-term changes in gut microbiota composition and more recently also with changes in the immune system. This has further been suggested to link Cesarean section (C-section) with an increased risk for development of immune-mediated diseases such as type 1 diabetes. In this study, we demonstrate that both C-section and cross-fostering with a genetically distinct strain influence the gut microbiota composition and immune key markers in mice. Gut microbiota profiling by denaturing gradient gel electrophoresis and 454/FLX-based 16S rRNA gene amplicon sequencing revealed that mice born by C-section had a distinct bacterial profile at weaning characterized by higher abundance of Bacteroides and Lachnospiraceae, and less Rikenellaceae and Ruminococcus. No clustering according to delivery method as determined by principal component analysis of denaturing gradient gel electrophoresis profiles was evident in adult mice. However, the adult C-section–born mice had lower proportions of Foxp3+ regulatory T cells, tolerogenic CD103+ dendritic cells, and less Il10 gene expression in mesenteric lymph nodes and spleens. This demonstrates long-term systemic effect on the regulatory immune system that was also evident in NOD mice, a model of type 1 diabetes, born by C-section. However, no effect of delivery mode was seen on diabetes incidence or insulitis development. In conclusion, the first exposure to microorganisms seems to be crucial for the early life gut microbiota and priming of regulatory immune system in mice, and mode of delivery strongly influences this.

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Dietary Xylooligosaccharide Downregulates IFN-γ and the Low-Grade Inflammatory Cytokine IL-1β Systemically in Mice

Cited by 81 publications

References 39 publications

Effect of Vitamin E Supplementation on Intestinal Barrier Function in Rats Exposed to High Altitude Hypoxia Environment

Effect of Vitamin E Supplementation on Intestinal Barrier Function in Rats Exposed to High Altitude Hypoxia Environment

A Maternal Gluten-Free Diet Reduces Inflammation and Diabetes Incidence in the Offspring of NOD Mice

Mode of Delivery Shapes Gut Colonization Pattern and Modulates Regulatory Immunity in Mice

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