普拉梭菌（Faecalibacterium prausnitzii）上调调节性 T 细胞和抗炎细胞因子治疗三硝基苯磺酸（TNBS）诱导的结肠炎。

Faecalibacterium prausnitzii upregulates regulatory T cells and anti-inflammatory cytokines in treating TNBS-induced colitis.

机构信息

Department of Gastroenterology, Peking University People Hospital, Beijing 100044, China; Department of Gastroenterology, Gulou School of Clinical Medicine, Nanjing Medical University, Nanjing 210008, China.

出版信息

J Crohns Colitis. 2013 Dec;7(11):e558-68. doi: 10.1016/j.crohns.2013.04.002. Epub 2013 May 2.

DOI:10.1016/j.crohns.2013.04.002

PMID:23643066

Abstract

BACKGROUND AND AIMS

Faecalibacterium prausnitzii (F. prausnitzii) is a common anaerobic bacteria colonized in the human gut and inflammatory bowel disease (IBD) patients are usually lack of F. prausnitzii. The aims of this study were to evaluate the anti-inflammatory and immunomodulatory capacity of F. prausnitzii by comparing it with Bifidobacterium longum (B. longum) in both cellular and animal experiments.

METHODS

Human peripheral blood mononuclear cells (PBMCs) and 2, 4, 6-trinitrobenzenesulphonic acid (TNBS)-induced colitis rat models were treated with F. prausnitzii, B. longum, F. prausnitzii supernatant or F. prausnitzii medium, respectively. Interleukin (IL)-10, TGF-β1 and IL-12p70 in human PBMCs culture supernatant and rat blood serum were detected. The frequency of CD25(+)Foxp3(+)Treg in human PBMCs, rat PBMCs and rat splenocytes were investigated. Besides, the T-bet, GATA-3, ROR-γt and Foxp3 mRNA in human PBMCs, histopathologic characteristics of the intestinal mucosal and weight loss in the rat models were examined.

RESULTS

F. prausnitzii, B. longum and F. prausnitzii supernatant clearly facilitated the induction of IL-10 and TGF-β1, while induced relatively mild production of IL-12p70 in both cellular and animal models. The F. prausnitzii, B. longum and supernatant differed in their capacity to induce T-bet, GATA-3 and ROR-γt mRNA expression in human PBMCs (both bacterial strains inhibited the expression of ROR-γt while supernatant inhibited the T-bet and GATA-3). However, all of them induced the Foxp3 and Treg production and ameliorated the TNBS-induced colitis. In addition, F. prausnitzii supernatant exhibited the supreme anti-inflammatory capacity.

CONCLUSIONS

F. prausnitzii and its unidentified metabolites in the supernatant are promising candidates in treating IBD, and further research remains necessary to elucidate the safety, efficacy, optimum and mechanism of this bacterium in the clinical practice.

摘要

背景和目的

普拉梭菌（Faecalibacterium prausnitzii，F. prausnitzii）是一种常见的定植于人类肠道的厌氧细菌，炎症性肠病（inflammatory bowel disease，IBD）患者通常缺乏普拉梭菌。本研究旨在通过细胞和动物实验比较普拉梭菌与长双歧杆菌（Bifidobacterium longum，B. longum）的抗炎和免疫调节能力。

方法

用人外周血单个核细胞（peripheral blood mononuclear cells，PBMCs）和 2,4,6-三硝基苯磺酸（2,4,6-trinitrobenzenesulphonic acid，TNBS）诱导的结肠炎大鼠模型分别用普拉梭菌、长双歧杆菌、普拉梭菌上清液或普拉梭菌培养基处理。检测人 PBMCs 培养上清液和大鼠血清中白细胞介素（interleukin，IL）-10、转化生长因子（transforming growth factor，TGF）-β1 和 IL-12p70 的水平。检测人 PBMCs、大鼠 PBMCs 和大鼠脾细胞中 CD25（+）Foxp3（+）Treg 的频率。此外，还检测了人 PBMCs 中的 T-bet、GATA-3、ROR-γt 和 Foxp3mRNA、大鼠肠道黏膜的组织病理学特征和大鼠的体重减轻情况。

结果

普拉梭菌、长双歧杆菌和普拉梭菌上清液均能明显促进细胞和动物模型中 IL-10 和 TGF-β1 的诱导，而相对轻度诱导 IL-12p70 的产生。普拉梭菌、长双歧杆菌和上清液在诱导人 PBMCs 中 T-bet、GATA-3 和 ROR-γt mRNA 表达方面存在差异（两种细菌株均抑制 ROR-γt 的表达，而上清液抑制 T-bet 和 GATA-3 的表达）。然而，它们都能诱导 Foxp3 和 Treg 的产生，并改善 TNBS 诱导的结肠炎。此外，普拉梭菌上清液表现出最强的抗炎能力。