Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients

被引:3276
作者
Sokol, Harry [2 ]
Pigneur, Benedicte [1 ]
Watterlot, Laurie [2 ]
Lakhdari, Omar [2 ]
Bermudez-Humaran, Luis G. [2 ]
Gratadoux, Jean-Jacques [2 ]
Blugeon, Sebastien [2 ]
Bridonneau, Chantal [2 ]
Furet, Jean-Pierre [2 ]
Corthier, Gerard [2 ]
Grangette, Corinne [3 ]
Vasquez, Nadia [4 ]
Pochart, Philippe [4 ]
Trugnan, Germain [1 ]
Thomas, Ginette [1 ]
Blottiere, Herve M. [2 ]
Dore, Joeel [2 ]
Marteau, Philippe [5 ]
Seksik, Philippe [1 ]
Langella, Philippe [2 ]
机构
[1] Univ Paris 06, Inst Natl Sante & Rech Med, U538, F-75571 Paris, France
[2] INRA, U910, Unite Ecol & Physiol Syst Digestif, F-78350 Jouy En Josas, France
[3] Inst Pasteur, Lab Bacteries Lact & Immun Muqueuses, F-59000 Lille, France
[4] Conservatoire Natl Arts & Metiers, Biol Lab, EA 3199, F-75003 Paris, France
[5] Hop Lariboisiere, AP HP, Gastroenterol Unit, F-75010 Paris, France
关键词
IBD; microbiota; probiotic;
D O I
10.1073/pnas.0804812105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
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 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.
引用
收藏
页码:16731 / 16736
页数:6
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