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
Hauptverfasser: Hayase, Eiko, Hayase, Tomo, Jamal, Mohamed A., Miyama, Takahiko, Chang, Chia-Chi, Ortega, Miriam R., Ahmed, Saira S., Karmouch, Jennifer L., Sanchez, Christopher A., Brown, Alexandria N., El-Himri, Rawan K., Flores, Ivonne I., McDaniel, Lauren K., Pham, Dung, Halsey, Taylor, Frenk, Annette C., Chapa, Valerie A., Heckel, Brooke E., Jin, Yimei, Tsai, Wen-Bin, Prasad, Rishika, Tan, Lin, Veillon, Lucas, Ajami, Nadim J., Wargo, Jennifer A., Galloway-Peña, Jessica, Shelburne, Samuel, Chemaly, Roy F., Davey, Lauren, Glowacki, Robert W. P., Liu, Chen, Rondon, Gabriela, Alousi, Amin M., Molldrem, Jeffrey J., Champlin, Richard E., Shpall, Elizabeth J., Valdivia, Raphael H., Martens, Eric C., Lorenzi, Philip L., Jenq, Robert R.
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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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2022.09.007