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

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.

SUBMITTER: Hayase E

PROVIDER: S-EPMC9542352 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Hayase Eiko E Hayase Tomo T Jamal Mohamed A MA Miyama Takahiko T Chang Chia-Chi CC Ortega Miriam R MR Ahmed Saira S SS Karmouch Jennifer L JL Sanchez Christopher A CA Brown Alexandria N AN El-Himri Rawan K RK Flores Ivonne I II McDaniel Lauren K LK Pham Dung D Halsey Taylor T Frenk Annette C AC Chapa Valerie A VA Heckel Brooke E BE Jin Yimei Y Tsai Wen-Bin WB Prasad Rishika R Tan Lin L Veillon Lucas L Ajami Nadim J NJ Wargo Jennifer A JA Galloway-Peña Jessica J Shelburne Samuel S Chemaly Roy F RF Davey Lauren L Glowacki Robert W P RWP Liu Chen C Rondon Gabriela G Alousi Amin M AM Molldrem Jeffrey J JJ Champlin Richard E RE Shpall Elizabeth J EJ Valdivia Raphael H RH Martens Eric C EC Lorenzi Philip L PL Jenq Robert R RR

Cell 20220901 20

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 ...[more]

PMID: 36179667

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Project description:Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occurring more than 2 years after HCT for malignant disease. Graft versus tumor (GVT) is a major component of the overall beneficial effects of allogeneic HCT in the treatment of hematological malignancies. Better understanding of GVHD pathogenesis is important to identify new therapeutic targets for GVHD prevention and therapy. Emerging data suggest opposing roles for different T cell subsets, e.g., IFN-γ producing CD4+ and CD8+ T cells (Th1 and Tc1), IL-4 producing T cells (Th2 and Tc2), IL-17 producing T cells (Th17 and Tc17), IL-9 producing T cells (Th9 and Tc9), IL-22 producing T cells (Th22), T follicular helper cells (Tfh), regulatory T-cells (Treg) and tissue resident memory T cells (Trm) in GVHD and GVT etiology. In this review, we first summarize the general description of the cytokine signals that promote the differentiation of T cell subsets and the roles of these T cell subsets in the pathogenesis of GVHD. Next, we extensively explore preclinical findings of T cell subsets in both GVHD/GVT animal models and humans. Finally, we address recent findings about the roles of T-cell subsets in clinical GVHD and current strategies to modulate T-cell differentiation for treating and preventing GVHD in patients. Further exploring and outlining the immune biology of T-cell differentiation in GVHD that will provide more therapeutic options for maintaining success of allo-HCT.

Dataset Information

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

Publications

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

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