Mucus-degrading Bacteroides link carbapenems to aggravated graft-versushost disease
The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broadspectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well-understood...
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Veröffentlicht in: | Cell 2022-09, Vol.185 (20), p.3705-3719.e14 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The intestinal microbiota is an important modulator of graft-versus-host
disease (GVHD), which often complicates allogeneic hematopoietic stem cell
transplantation (allo-HSCT). Broadspectrum 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 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 degradation of mucin
glycans. These mice also had thinning of the colonic mucus layer and decreased
levels of xylose in colon 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 antibioticmediated microbiome injury
to reduce the risk for intestinal GVHD in allo-HSCT patients.
Antibiotic usage increases the risk for graft-versus-host disease (GVHD),
a complication of hematopoietic stem cell transplantation, through the expansion
of the colonic mucus-degrading gut microbe Bacteroides thetaiotaomicron.
Supplementation oral xylose reduces thinning of the colonic mucus layer in mice
and may be an option to reduce GVHD. |
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ISSN: | 0092-8674 1097-4172 |
DOI: | 10.1016/j.cell.2022.09.007 |