近日，美国德克萨斯大学教授Robert R. Jenq及其研究小组发现，粘液层降解型拟杆菌将碳青霉烯类药物与移植物抗宿主疾病的加重联系起来。相关论文发表在2022年9月29日出版的《细胞》杂志上。

研究人员表示，肠道微生物群是移植物抗宿主疾病（GVHD）的一个重要调节因子，它常常使异体造血干细胞移植（allo-HSCT）变得复杂。广谱抗生素如碳青霉烯类药物会增加肠道GVHD的风险，但其机制并不十分清楚。

研究人员发现用美罗培南（一种常用的碳青霉烯类药物）治疗小鼠时，会通过增加多形拟杆菌（BT）而加重结肠GVHD。BT具有降解食物多糖和宿主粘蛋白糖的广泛能力。经美罗培南处理的同种异体小鼠的BT表现出粘蛋白糖降解酶的表达上调。这些小鼠的结肠粘液层也变薄，结肠腔内容物中木糖的水平下降。有趣的是，口服木糖补充剂可以明显防止美罗培南处理的小鼠结肠粘液层变薄。特定的营养补充策略，包括木糖补充，可以对抗抗生素介导的微生物组损伤，从而减少异体造血干细胞移植患者的肠道GVHD风险。

附：英文原文

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

Author: 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 Tsai, Rishika Prasad, Lin Tan, Lucas Veillon, Nadim J. Ajami, Jennifer A. Wargo, Jessica Galloway-Pea, 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

Issue&Volume: 2022/09/29

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 withmeropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansionof 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 enzymesinvolved in the degradation of mucin glycans. These mice also had thinning of thecolonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly,oral xylose supplementation significantly prevented thinning of the colonic mucuslayer in meropenem-treated mice. Specific nutritional supplementation strategies,including xylose supplementation, may combat antibiotic-mediated microbiome injuryto reduce the risk for intestinal GVHD in allo-HSCT patients.

DOI: 10.1016/j.cell.2022.09.007

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01129-1