title: Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation.
abstract: Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. jenqr@mskcc.org
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jenq
authors.forename: Carles
authors.initials: C
authors.lastname: Ubeda
authors.forename: Ying
authors.initials: Y
authors.lastname: Taur
authors.forename: Clarissa C
authors.initials: CC
authors.lastname: Menezes
authors.forename: Raya
authors.initials: R
authors.lastname: Khanin
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Dudakov
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Mallory L
authors.initials: ML
authors.lastname: West
authors.forename: Natalie V
authors.initials: NV
authors.lastname: Singer
authors.forename: Michele J
authors.initials: MJ
authors.lastname: Equinda
authors.forename: Asia
authors.initials: A
authors.lastname: Gobourne
authors.forename: Lauren
authors.initials: L
authors.lastname: Lipuma
authors.forename: Lauren F
authors.initials: LF
authors.lastname: Young
authors.forename: Odette M
authors.initials: OM
authors.lastname: Smith
authors.forename: Arnab
authors.initials: A
authors.lastname: Ghosh
authors.forename: Alan M
authors.initials: AM
authors.lastname: Hanash
authors.forename: Jenna D
authors.initials: JD
authors.lastname: Goldberg
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Aoyama
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000667:Ampicillin; D000818:Animals; D001483:Base Sequence; D044822:Biodiversity; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016264:Dextran Sulfate; D004760:Enterocolitis / Q000209:etiology / Q000382:microbiology* / Q000473:pathology; D005243:Feces / Q000382:microbiology; D006086:Graft vs Host Disease / Q000150:complications* / Q000382:microbiology; D006094:Gram-Positive Bacteria / Q000302:isolation & purification; D006801:Humans; D054892:Metagenome / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014184:Transplantation, Homologous
chemical_list: D012336:RNA, Ribosomal, 16S; D000667:Ampicillin; D016264:Dextran Sulfate