Ecobiotherapy Rich in Firmicutes Decreases Susceptibility to Colitis in a Humanized Gnotobiotic Mouse Model. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: Natividad, Jane M.; Pinto-Sanchez, Maria I.; Galipeau, Heather J.; Jury, Jennifer; Jordana, Manel; Reinisch, Walter; Collins, Stephen M.; Bercik, Premsyl; Surette, Michael G.; Allen-Vercoe, Emma; Verdu, Elena F.
• Is Part Of: Inflammatory bowel diseases. Volume 21:Issue 8(2015:Aug.)
• Publication Date: 2015-08
• Subjects: ulcerative colitis -- microbiota -- TH17 -- Firmicutes; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000422
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: Alterations in the intestinal microbiota, characterized by depletion of anti-inflammatory bacteria, such as Firmicutes, in patients with ulcerative colitis (UC) have prompted interest in microbiota-modulating strategies for this condition. The aim of this study was to evaluate the role of fecal and synthetic human microbial ecosystems, low or enriched in Firmicutes, on colitis susceptibility and host immune responses. Methods: The microbiota of selected healthy and UC human donors was characterized by culture method and 16S rRNA-based sequencing. Germ-free mice were colonized with fecal or a synthetic ecosystem enriched (healthy donors) or low (UC donors) in Firmicutes. Experimental colitis was induced using dextran sodium sulfate. Colon transcriptome and colon lamina propria cells were evaluated in mice postcolonization by RNA-seq and flow cytometry, respectively, and T helper (TH ) 17 differentiation was assessed in vitro. Results: Mice colonized with microbiota from patients with UC low in Firmicutes had increased sensitivity to colitis compared with mice colonized with fecal or synthetic ecosystems rich in Firmicutes. Microbiota low in Firmicutes increased expression of TH 17-related genes and expansion of interleukin-17A–expressing CD4 + cells in vivo. Supplementation with bacterial isolates belonging to the Firmicutes phylum abrogated the heightened TH 17 responses in vitro. Conclusions: A microbiota rich in Firmicutes derived from fecal samples of a healthy human donor, or assembled synthetically, downregulated colonic inflammation and TH 17 pathways in mice. The results support the use of ecobiotherapy strategies, enriched in Firmicutes, for the prevention or treatment of UC. Abstract : Article first published online 29 April 2015.Supplemental Digital Content is Available in the Text.