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The abundance of Faecalibacterium prausnitzii, an abundant and representative bacterium of Firmicutes phylum, has consistently been observed to be lower in patients with Crohn's disease than in healthy individuals. We have shown that both F. prausnitzii and its culture supernatant (SN) have anti-inflammatory and protective effects in a TNBS-induced acute colitis mouse model. Here, we tested the effects of both F. prausnitzii and its SN in moderate and severe DNBS-induced chronic colitis mouse models.Colitis was induced by intrarectal administration of DNBS. After either 4 or 10 days of recovery (severe and moderate protocols, respectively), groups of mice were intragastrically administered either with F. prausnitzii A2-165 or with its culture SN for 7 or 10 days. Three days before being sacrificed, colitis was reactivated by administration of a lower dose of DNBS. The severity of colitis at the time of being sacrificed was assessed by weight loss and macroscopic and microscopic scores. Myeloperoxidase (MPO) activity, cytokine levels, lymphocyte populations, and changes in microbiota were studied.Intragastric administration of either F. prausnitzii or its SN led to a significant decrease in colitis severity in both severe and moderate chronic colitis models. The lower severity of colitis was associated with down-regulation of MPO, pro-inflammatory cytokines, and T-cell levels.We show, for the first time, protective effects of both F. prausnitzii and its SN during both the period of recovery from chronic colitis and colitis reactivation. These results provide further evidence that F. prausnitzii is an anti-inflammatory bacterium with therapeutic potential for patients with inflammatory bowel disease.