Faculty, Staff and Student Publications
Publication Date
9-29-2022
Journal
Cell
Abstract
The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.
Keywords
Animals, Anti-Bacterial Agents, Bacteroides, Carbapenems, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Meropenem, Mice, Mucins, Mucus, Polysaccharides, Xylose, Mucus-degrading bacteria, Bacteroides, Bacteroides thetaiotaomicron, allogeneic hematopoietic stem cell transplantation, graft-versus-host disease, broad-spectrum antibiotics, carbapenem, xylose, mucus layer, intestinal microbiome
DOI
10.1016/j.cell.2022.09.007
PMID
36179667
PMCID
PMC9542352
PubMedCentral® Posted Date
9-29-2023
PubMedCentral® Full Text Version
Author MSS
Graphical Abstract
Published Open-Access
yes
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Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons