Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease Journal Article

   


Authors: Mathewson, N. D.; Jenq, R.; Mathew, A. V.; Koenigsknecht, M.; Hanash, A.; Toubai, T.; Oravecz-Wilson, K.; Wu, S. R.; Sun, Y. P.; Rossi, C.; Fujiwara, H.; Byun, J.; Shono, Y.; Lindemans, C.; Calafiore, M.; Schmidt, T. C.; Honda, K.; Young, V. B.; Pennathur, S.; van den Brink, M.; Reddy, P.
Article Title: Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease
Abstract: The effect of alterations in intestinal microbiota on microbial metabolites and on disease processes such as graft-versus-host disease (GVHD) is not known. Here we carried out an unbiased analysis to identify previously unidentified alterations in gastrointestinal microbiota-derived short-chain fatty acids (SCFAs) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amount of only one SCFA, butyrate, were observed only in the intestinal tissue. The reduced butyrate in CD326(+) intestinal epithelial cells (IECs) after allo-BMT resulted in decreased histone acetylation, which was restored after local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate-producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate disease severity.
Keywords: hypertension; colon; regulatory t-cells; bone-marrow-transplantation; stem-cell; permeability; gastrointestinal-tract; sodium-butyrate; chain fatty-acids; histone deacetylase inhibition
Journal Title: Nature Immunology
Volume: 17
Issue: 5
ISSN: 1529-2908
Publisher: Nature Publishing Group  
Date Published: 2016-05-01
Start Page: 505
End Page: 513
Language: English
ACCESSION: WOS:000374323100009
DOI: 10.1038/ni.3400
PROVIDER: wos
PMCID: PMC4836986
PUBMED: 26998764
Notes: Article -- Source: Wos
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MSK Authors
  1. Marcel R M Van Den Brink
    616 Van Den Brink
  2. Alan M Hanash
    119 Hanash
  3. Robert R Jenq
    107 Jenq
  4. Yusuke Shono
    39 Shono
  5. Caroline Ariane Lindemans
    8 Lindemans
  6. Marco Calafiore
    25 Calafiore
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