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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