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

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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., Singer, Natalie V., Equinda, Michele J., Gobourne, Asia, Lipuma, Lauren, Young, Lauren F., Smith, Odette M., Ghosh, Arnab, Hanash, Alan M., Goldberg, Jenna D., Aoyama, Kazutoshi, Blazar, Bruce R., Pamer, Eric G., R.M. van den Brink, Marcel·2012·Journal of Experimental Medicine

DOI 10.1084/jem.20112408PMC PMC3348096

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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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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.
ORCID: Jenq, Robert R.
Taur, Ying
Dudakov, Jarrod A.
Liu, Chen
Lipuma, Lauren
Young, Lauren F.
Ghosh, Arnab
Hanash, Alan M.
Blazar, Bruce R.
Pamer, Eric G.
Venue: Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2012-04-30
Volume: 209
Issue: 5
Pages: 903-911
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20112408
PMC: PMC3348096
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: green
www.ncbi.nlm.nih.gov
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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Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation

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