title: Ecobiotherapy Rich in Firmicutes Decreases Susceptibility to Colitis in a Humanized Gnotobiotic Mouse Model.
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 TH17-related genes and expansion of interleukin-17A-expressing CD4 cells in vivo. Supplementation with bacterial isolates belonging to the Firmicutes phylum abrogated the heightened TH17 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 TH17 pathways in mice. The results support the use of ecobiotherapy strategies, enriched in Firmicutes, for the prevention or treatment of UC.
authors.affiliation: *Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada; †Department of Pathology, and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; and ‡Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Natividad
authors.forename: Maria I
authors.initials: MI
authors.lastname: Pinto-Sanchez
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Galipeau
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jury
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Collins
authors.forename: Premsyl
authors.initials: P
authors.lastname: Bercik
authors.forename: Michael G
authors.initials: MG
authors.lastname: Surette
authors.forename: Emma
authors.initials: E
authors.lastname: Allen-Vercoe
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005243:Feces / Q000382:microbiology*; D005260:Female; D000068536:Bacillota / Q000502:physiology*; D005434:Flow Cytometry; D005856:Germ-Free Life; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota