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米糠中的新型益生元通过调节肠道内稳态和黏膜免疫系统改善小鼠结肠炎模型中的炎症。

New prebiotics from rice bran ameliorate inflammation in murine colitis models through the modulation of intestinal homeostasis and the mucosal immune system.

作者信息

Komiyama Yutaka, Andoh Akira, Fujiwara Daisuke, Ohmae Hideo, Araki Yoshio, Fujiyama Yoshihide, Mitsuyama Keiichi, Kanauchi Osamu

机构信息

Kirin Holdings Co., Central Labs for Frontier Technology, 1-13-5 Fukuura Kanazawa-ku, Yokohama, Japan.

出版信息

Scand J Gastroenterol. 2011 Jan;46(1):40-52. doi: 10.3109/00365521.2010.513062. Epub 2010 Aug 24.

Abstract

BACKGROUND

Enzyme-treated rice fiber (ERF) is a recently developed prebiotic product made from rice bran by heat-resistant amylase, protease and hemicellulase treatment. Although the detailed mechanism of inflammatory bowel disease (IBD) is still unclear, the role of the resident luminal bacteria and its interaction on the mucosal barrier seem to be an important factor in the development of IBD and its chronicity. With the objective of manipulating the intestinal microbiota in IBD, this study was carried out to evaluate the effects of ERF on IBD with using experimental colitis models.

METHODS

Three colitis models were used and they were induced by the oral administration of dextran sodium sulfate in male Sprague-Dawley rats or BALB/c mice and transferring CD4+ CD45RB(high) T cells to female SCID mice, sequentially their CD4+ T cells were retransferred to new SCID mice. The evaluation included the measurement of body weight, spleen weight, colon length, histological examination, serum and mucosal cytokine (tumor necrosis factor-alpha (TNF-α), an interferon-gamma (IFN-γ), interleukin-12 p70 (IL-12p70), IL-1β, IL-6, IL-4) analysis, mucosal serotonin (5HT), and organic acid production and a microbiota analysis of the cecal contents. The characteristics of T cell surface markers including CD4, CD69, CD45RB of spleen and mesenteric lymph nodes (MLN) were also analyzed. In addition, the effects of ERF on the change in the induction of dendritic cells (DCs) were evaluated.

RESULTS

The preventive effect of ERF on colitis was significantly superior to that of raw material rice bran or control group. An overexpression of inflammatory cytokine production was attenuated by ERF treatment, which was accompanied with a decrease in both the colonic mucosal damage and 5HT production. Furthermore, ERF significantly attenuated the T cell activation (CD4+CD69+) of spleen and MLN, and this characteristic was inherited by the retransferred mice. ERF significantly suppressed the growth of Clostiridium, and increased short-chain fatty acids (acetate, propionate and butyrate) content in colitis. The relatively hydrophilic fraction of ERF (ethanol-methanol soluble fraction) is therefore considered to have a potent ability to attenuate the induction of DCs.

CONCLUSION

A new prebiotic, ERF, reduced inflammation by modulating the colonic environment and regulating immune cell differentiation. Although a more detailed study is required, this study showed the promising anti-inflammatory effects of an adjunctive prebiotic treatment for IBD.

摘要

背景

酶处理米纤维(ERF)是一种最近开发的益生元产品,由米糠经耐热淀粉酶、蛋白酶和半纤维素酶处理制成。虽然炎症性肠病(IBD)的详细机制仍不清楚,但肠道常驻细菌的作用及其与黏膜屏障的相互作用似乎是IBD发生及其慢性化的一个重要因素。为了调控IBD患者的肠道微生物群,本研究利用实验性结肠炎模型评估了ERF对IBD的影响。

方法

使用了三种结肠炎模型,分别通过给雄性斯普拉格-道利大鼠或BALB/c小鼠口服葡聚糖硫酸钠,以及将CD4+CD45RB(高)T细胞转移到雌性SCID小鼠体内,随后将其CD4+T细胞重新转移到新的SCID小鼠体内来诱导。评估内容包括体重、脾脏重量、结肠长度的测量,组织学检查,血清和黏膜细胞因子(肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白细胞介素-12 p70(IL-12p70)、IL-1β、IL-6、IL-4)分析,黏膜5-羟色胺(5HT)、有机酸产生以及盲肠内容物的微生物群分析。还分析了脾脏和肠系膜淋巴结(MLN)中T细胞表面标志物(包括CD4、CD69、CD45RB)的特征。此外,评估了ERF对树突状细胞(DCs)诱导变化的影响。

结果

ERF对结肠炎的预防作用明显优于原料米糠或对照组。ERF处理可减轻炎症细胞因子产生的过度表达,同时结肠黏膜损伤和5HT产生均减少。此外,ERF显著减轻了脾脏和MLN中T细胞的活化(CD4+CD69+),并且这种特征可被重新转移的小鼠继承。ERF显著抑制了梭菌的生长,并增加了结肠炎中短链脂肪酸(乙酸、丙酸和丁酸)的含量。因此,ERF相对亲水的部分(乙醇-甲醇可溶部分)被认为具有减弱DCs诱导的强大能力。

结论

一种新型益生元ERF通过调节结肠环境和免疫细胞分化来减轻炎症。尽管需要更详细的研究,但本研究显示了辅助益生元治疗IBD具有良好的抗炎效果。

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