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-kappaB activity, F. prausnitzii had no effect on IL-1beta-induced NF-kappaB 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-kappaB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.
Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.
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作者:Sokol Harry, Pigneur Bénédicte, Watterlot Laurie, Lakhdari Omar, Bermúdez-Humarán Luis G, Gratadoux Jean-Jacques, Blugeon Sébastien, Bridonneau Chantal, Furet Jean-Pierre, Corthier Gérard, Grangette Corinne, Vasquez Nadia, Pochart Philippe, Trugnan Germain, Thomas Ginette, Blottière Hervé M, Doré Joël, Marteau Philippe, Seksik Philippe, Langella Philippe
| 期刊: | Proceedings of the National Academy of Sciences of the United States of America | 影响因子: | 9.100 |
| 时间: | 2008 | 起止号: | 2008 Oct 28; 105(43):16731-6 |
| doi: | 10.1073/pnas.0804812105 | ||
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