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

Cell. 2022 Sep 29;185(20):3705-3719.e14. doi: 10.1016/j.cell.2022.09.007.

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: Bacteroides; Bacteroides thetaiotaomicron; allogeneic hematopoietic stem cell transplantation; broad-spectrum antibiotics; carbapenem; graft-versus-host disease; intestinal microbiome; mucus layer; mucus-degrading bacteria; xylose.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacteroides
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation*
  • Meropenem
  • Mice
  • Mucins / metabolism
  • Mucus / metabolism
  • Polysaccharides / metabolism
  • Xylose

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Mucins
  • Polysaccharides
  • Xylose
  • Meropenem