普氏粪杆菌
结肠炎
失调
炎症性肠病
肠粘膜
微生物群
双歧杆菌
微生物学
克罗恩病
促炎细胞因子
厚壁菌
生物
免疫学
人体微生物群
溃疡性结肠炎
粪便
普雷沃菌属
肠道菌群
医学
细菌
炎症
乳酸菌
内科学
疾病
16S核糖体RNA
遗传学
作者
Harry Sokol,Bénédicte Pigneur,Laurie Watterlot,Omar Lakhdari,Luis G. Bermúdez‐Humarán,Jean-Jacques Gratadoux,Sébastien Blugeon,Chantal Bridonneau,Jean-Pierre Furet,Gérard Corthier,Corinne Grangette,Nadia Vasquez,Philippe Pochart,Germain Trugnan,G. Thomas,Hervé M. Blottière,Joël Doré,Philippe Marteau,Philippe Seksik,Philippe Langella
标识
DOI:10.1073/pnas.0804812105
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-κB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-γ 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.
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