Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients
Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients
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DOI：
10.1073/pnas.0804812105
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发表时间：
2008-10-28
影响因子：
11.1
通讯作者：
Langella, Philippe
中科院分区：
文献类型：
--
作者：
Sokol, Harry;Pigneur, Benedicte;Langella, Philippe
在克罗恩病（CD）患者中反复观察到优势厚壁菌门内肠道细菌的丰度和生物多样性下降。在这项研究中，我们使用FISH分析确定了CID患者在手术切除时和6个月后的粘膜相关微生物群的组成。我们发现厚壁菌门的主要成员普氏粪杆菌的减少与回肠CID术后复发的风险较高相关。F. prausnitzii对切除的回肠克罗恩病粘膜的作用也与6个月时内镜下复发有关。评价F. prausnitzii的抗炎作用。prausnitzii在体外（细胞模型）和体内[2，4，6-三硝基苯磺酸（TNBS）诱导的]小鼠结肠炎中的作用。在转染NF-κ B B活性报告基因的Caco-2细胞中，F. prausnitzii对IL-1 β诱导的NF-κ B活性无影响，而培养上清则能抑制IL-1 β诱导的NF-κ B活性。prausnitzii导致显著降低的IL-12和IFN-γ产生水平和较高的IL-10分泌。口服活F. prausnitzii或其上清液显著降低TNBS结肠炎的严重程度，并倾向于纠正与TNBS结肠炎相关的生态失调，如通过实时定量PCR（qPCR）分析所证明的。F. prausnitzii对细胞和TNBS结肠炎模型表现出抗炎作用，部分原因是分泌的代谢物能够阻断NF-κ B活化和IL-8产生。这些结果表明，使用F. prausnitzii作为益生菌在CID治疗中是一种有前途的策略。
A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CID patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CID. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-kappa B activity, F. prausnitzii had no effect on IL-1 beta-induced NF-kappa B activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-gamma production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-kappa B activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CID treatment.