Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease

Eiko Hayase, Tomo Hayase, Mohamed A. Jamal, Takahiko Miyama, Chia Chi Chang, Miriam R. Ortega, Saira S. Ahmed, Jennifer L. Karmouch, Christopher A. Sanchez, Alexandria N. Brown, Rawan K. El-Himri, Ivonne I. Flores, Lauren K. McDaniel, Dung Pham, Taylor Halsey, Annette C. Frenk, Valerie A. Chapa, Brooke E. Heckel, Yimei Jin, Wen Bin TsaiRishika Prasad, Lin Tan, Lucas Veillon, Nadim J. Ajami, Jennifer A. Wargo, Jessica Galloway-Peña, Samuel Shelburne, Roy F. Chemaly, Lauren Davey, Robert W.P. Glowacki, Chen Liu, Gabriela Rondon, Amin M. Alousi, Jeffrey J. Molldrem, Richard E. Champlin, Elizabeth J. Shpall, Raphael H. Valdivia, Eric C. Martens, Philip L. Lorenzi, Robert R. Jenq

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)3705-3719.e14
JournalCell
Volume185
Issue number20
DOIs
Publication statusPublished - 29-09-2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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