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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Faecalibacterium Prausnitzii Is An Anti-inflammatory Commensal Bacterium Identified By Gut Microbiota Analysis Of Crohn Disease Patients
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Faecalibacterium Prausnitzii Is An Anti-inflammatory Commensal Bacterium Identified By Gut Microbiota Analysis Of Crohn Disease Patients

机译：Faecalibacterium Prausnitzii是一种通过克罗恩病患者肠道菌群分析鉴定的抗炎共生细菌

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摘要

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 CD 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 CD. 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-κB activity, F. prausnitzii had no effect on IL-1β-induced NF-kB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-y 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-κB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.
机译：在克罗恩病（CD）患者中反复观察到优势菌门纤毛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CD患者在手术切除时和6个月后与粘膜相关的微生物群的组成。我们发现，Fimicutes的主要成员Faecalibacterium prausnitzii的减少与回肠CD术后复发的较高风险相关。在切除的回肠克罗恩粘膜上，F。prausnitzii的比例较低也与6个月内镜复发有关。为了评估F. prausnitzii的免疫调节特性，我们分析了F. prausnitzii在小鼠体外（细胞模型）和体内[2,4,6-三硝基苯磺酸（TNBS）诱导的]结肠炎的抗炎作用。在转染了报告基因的NF-κB活性的Caco-2细胞中，普劳氏梭菌对IL-1β诱导的NF-kB活性没有影响，而上清液则将其废除了。 F. prausnitzii对体外外周血单核细胞的刺激导致IL-12和IFN-γ的产生水平显着降低，IL-10的分泌增加。实时定量PCR（qPCR）分析表明，口服活产普氏假单胞菌或其上清液可显着降低TNBS结肠炎的严重程度，并倾向于纠正与TNBS结肠炎相关的营养不良。 F. prausnitzii对细胞和TNBS结肠炎模型表现出抗炎作用，部分是由于分泌的代谢产物能够阻断NF-κB激活和IL-8产生。这些结果表明，使用F.prausnitzii作为益生菌来平衡营养不良是CD治疗中有希望的策略。

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