Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation Journal Article


Authors: Jenq, R. R.; Ubeda, C.; Taur, Y.; Menezes, C. C.; Khanin, R.; Dudakov, J. A.; Liu, C.; West, M. L.; Singer, N. V.; Equinda, M. J.; Gobourne, A.; Lipuma, L.; Young, L. F.; Smith, O. M.; Ghosh, A.; Hanash, A. M.; Goldberg, J. D.; Aoyama, K.; Blazar, B. R.; Pamer, E. G.; van den Brink, M. R. M.
Article 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. © 2012 Jenq et al.
Keywords: controlled study; human tissue; treatment outcome; transplantation, homologous; genetics; nonhuman; methotrexate; molecular genetics; mouse; animal; animals; mice; animal tissue; disease association; animal experiment; animal model; allogenic bone marrow transplantation; pathology; risk factor; disease severity; molecular sequence data; species specificity; nucleotide sequence; graft versus host reaction; enteritis; species difference; base sequence; dna sequence; methylprednisolone; enterococcus; intestine flora; microbiology; calcineurin inhibitor; bone marrow transplantation; graft vs host disease; mycophenolic acid 2 morpholinoethyl ester; rna 16s; isolation and purification; metronidazole; quinoline derived antiinfective agent; antibiotic prophylaxis; feces; rapamycin; graft recipient; allotransplantation; sequence analysis, dna; phylogeny; enterocolitis; budesonide; biodiversity; gram positive bacterium; paneth cell; ampicillin; metagenome; streptococcus; dextran sulfate; gram-positive bacteria; rna, ribosomal, 16s; clostridiales; lactobacillales
Journal Title: Journal of Experimental Medicine
Volume: 209
Issue: 5
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2012-05-07
Start Page: 903
End Page: 911
Language: English
DOI: 10.1084/jem.20112408
PROVIDER: scopus
PMCID: PMC3348096
PUBMED: 22547653
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 24 August 2012" - "CODEN: JEMEA" - "Source: Scopus"
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MSK Authors
  1. Eric Pamer
    266 Pamer
  2. Alan M Hanash
    88 Hanash
  3. Jarrod Andrew Dudakov
    58 Dudakov
  4. Robert R Jenq
    103 Jenq
  5. Arnab Ghosh
    47 Ghosh
  6. Raya Khanin
    40 Khanin
  7. Ying Taur
    101 Taur
  8. Odette Marsinay Smith
    95 Smith
  9. Lauren Young
    39 Young
  10. Lauren Beth Lipuma
    14 Lipuma
  11. Natalie Singer
    24 Singer
  12. Mallory Lia West
    24 West