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粪便微生物群移植对小鼠溃疡性结肠炎的有益作用

Beneficial Effects of Fecal Microbiota Transplantation on Ulcerative Colitis in Mice.

作者信息

Tian Zhihui, Liu Jie, Liao Mengyu, Li Wenjuan, Zou Jiaqi, Han Xinxin, Kuang Mingjie, Shen Wanqiu, Li Haidong

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.

Department of Chemical Biology, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.

出版信息

Dig Dis Sci. 2016 Aug;61(8):2262-2271. doi: 10.1007/s10620-016-4060-2. Epub 2016 Feb 5.

Abstract

BACKGROUND

Ulcerative colitis (UC) is a chronic condition and the most common form of inflammatory bowel disease. The goal of standard treatment is mainly to induce and maintain remission with anti-inflammatory, immunosuppressive agents, and/or colectomy. Fecal microbiota transplantation (FMT) has been used successfully to treat relapsing or refractory Clostridium difficile infection. The alteration of microbiota in mouse models of UC as well as in patients suggested the possibility of treating UC with FMT.

AIMS

To study the effects of FMT on dextran sodium sulfate (DSS)-induced UC model in mice.

METHODS

Littermates of BALB/c and C57BL/6J were randomized into four groups: normal control , treatment with DSS for 7 days (DSS - FMT), treatment with DSS followed by FMT for another 8 days (DSS + FMT), and treatment with DSS and FMT followed by another 5 days for recovery (remission). Body weight, survival rate, and DAI scores of mice in each group were recorded. Changes in distal colon were studied by histopathology. Alterations of spleen and lamina propria regulatory lymphocytes, major bacterial species in feces and inflammatory cytokines in colon were also studied.

RESULTS

C57BL/6J mice experienced more significant weight loss than BALB/c mice after DSS treatment, regardless of whether the two strains of mice were co-housed or not. FMT caused reversal of DAI scores in BALB/c but not in C57BL/6J mice. In BALB/c mice, FMT also reduced colon inflammation that was paralleled by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulatory lymphocyte proportions.

CONCLUSIONS

FMT is effective in a mouse model of UC through its modulation on gut microbiota and the host immune system.

摘要

背景

溃疡性结肠炎(UC)是一种慢性疾病,也是炎症性肠病最常见的形式。标准治疗的目标主要是使用抗炎、免疫抑制剂和/或结肠切除术诱导并维持缓解。粪便微生物群移植(FMT)已成功用于治疗复发性或难治性艰难梭菌感染。UC小鼠模型以及患者体内微生物群的改变提示了用FMT治疗UC的可能性。

目的

研究FMT对葡聚糖硫酸钠(DSS)诱导的小鼠UC模型的影响。

方法

将BALB/c和C57BL/6J同窝小鼠随机分为四组:正常对照组、用DSS处理7天(DSS - FMT)、用DSS处理后再进行8天FMT(DSS + FMT)以及用DSS和FMT处理后再恢复5天(缓解)。记录每组小鼠的体重、存活率和疾病活动指数(DAI)评分。通过组织病理学研究远端结肠的变化。还研究了脾脏和固有层调节性淋巴细胞的变化、粪便中的主要细菌种类以及结肠中的炎性细胞因子。

结果

无论两种品系的小鼠是否同笼饲养,DSS处理后C57BL/6J小鼠的体重减轻比BALB/c小鼠更显著。FMT使BALB/c小鼠的DAI评分逆转,但对C57BL/6J小鼠无效。在BALB/c小鼠中,FMT还减轻了结肠炎症,同时炎症细胞因子水平降低、细菌微生物群改变以及调节性淋巴细胞比例改变。

结论

FMT通过调节肠道微生物群和宿主免疫系统在UC小鼠模型中有效。

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