Gut microbiome derived metabolites modulate intestinal epithelial cell damage and mitigate Graft-versus-Host Disease
By N. Mathewson, Robert R. Jenq, A. Mathew, M. Koenigsknecht, A. Hanash, T. Toubai, K. Oravecz-Wilson, Shin-Rong Wu, Yaping Sun, C. Rossi and 11 more. Nature Immunology, 2016
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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.
Subfields: Hematology, Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/566fce6062ceb85007cc488721d8da777b099736
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Citations in the corpus
- Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis (2022, background): “Butyrate provides energy, maintains the integrity of colonocytes, enhances the barrier function [48], and increases mucin expression, via MUC2 gene expression [49].”
- Short-chain fatty acids: linking diet, the microbiome and immunity (2024, positive): “Reduced butyrate levels are strongly associated with acute GVHD in patients after allogeneic HSCT 201 and with paediatric HSCT recipients who later develop chronic GVHD 202 .”
- Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers (2018, background): “It may be protective against several diseases, including colorectal cancer (5), inflammatory bowel disease (6), graft-versus-host disease (7), diabetes (8), and obesity (8, 9).”
- Microbiota in health and diseases (2022, background): “3, butyrates are involved in mediating the integrity of the intestinal barrier and are suggested to have direct salutary effects on intestinal epithelial cells.(135) Propionates are mainly oxidized or metabolized in the liver.”