Cited by 626Gut microbiota and healthHematopoietic Stem Cell TransplantationProbiotics and Fermented Foods

Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation

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Jenq, Robert R., Ubeda, Carles, Taur, Ying, Menezes, Clarissa C., Khanin, Raya, Dudakov, Jarrod A., Liu, Chen, West, Mallory L. +13 more·2012·Journal of Experimental Medicine

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.

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  • Animal models indicate that commensal bacteria affect GVHD pathophysiology.

    “Preclinical models have shown that commensal bacteria influence the pathophysiology of GVHD.10,17–20”
  • Acute GVHD onset is associated with loss of microbial diversity, reduction of Faecalibacterium, Ruminococcus, Lactobacillus and Blautia, and enrichment of Enterococcus and Clostridiales.

    “The onset of acute-GVHD is associated with significant shifts in the composition of the microbiota with a loss of overall diversity and reduction of health-promoting obligate anaerobes such as Faecalibacterium, Ruminococcus, Lactobacillus, and Blautia, and an enrichment of Enterococcus and Clostridiales”

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  1. Ubeda C. Taur Y. Jenq R.R. Equinda M.J. Son T. Samstein M. Viale A. Socci N.D. van den Brink M.R.M. Kamboj M. Pamer E.G. 2010 Intestinal domination by Vancomycin-resistant Enterococcus precedes bloodstream invasion in humans. J. Clin. Invest. In press PMC2993598 21099116

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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., & R.M. van den Brink, M.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Adult Bone Marrow Transplantation Service 1 and 2 ; and 3
  • Cornell University (US)
  • University of Florida (US)
  • University of Minnesota (US)
Corresponding author
Jenq, Robert R.
Venue
Journal of Experimental Medicine
Published
2012-04-30
Volume
209
Issue
5
Pages
903-911
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2131766513
Cited by
626
References
37
Citations by year
2026: 15 · 2025: 35 · 2024: 23 · 2023: 45 · 2022: 55 · 2021: 53 · 2020: 58 · 2019: 48 · 2018: 51 · 2017: 67 · 2016: 61 · 2015: 40 · 2014: 43 · 2013: 22 · 2012: 10
FWCI
14.69
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (UL1TR000064, 4r37ai039031-21, 5k23ai095398-05)
  • National Heart, Lung, and Blood Institute (R01HL056067, R01HL069929)
  • National Cancer Institute (P01CA023766, P01CA142106, R01CA107096, P30CA008748)
  • National Institute of Allergy and Infectious Diseases (R01AI034495, R37-AI039031, R01AI100288, R01AI080455, K23-AI095398, P01AI056299, R01AI042135)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
intestinal inflammation, gut microbiota, allogeneic bone marrow transplantation, graft-versus-host disease, Lactobacillus, Lactobacillales, Clostridiales, microbial diversity, microbiome manipulation, gut microbiota composition
MeSH terms
Ampicillin, Animals, Base Sequence, Enterocolitis, Feces, Graft vs Host Disease, Gram-Positive Bacteria, Humans, Molecular Sequence Data, Phylogeny, RNA, Ribosomal, 16S, Species Specificity, Transplantation, Homologous, Bone Marrow Transplantation, Dextran Sulfate, Sequence Analysis, DNA, Biodiversity, Mice, Metagenome

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