缓解失调微生物群诱导的肠道移植物抗宿主病。

alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease.

作者信息

Hayase Eiko, Hayase Tomo, Mukherjee Akash, Stinson Stuart C, Jamal Mohamed A, Ortega Miriam R, Sanchez Christopher A, Ahmed Saira S, Karmouch Jennifer L, Chang Chia-Chi, Flores Ivonne I, McDaniel Lauren K, Brown Alexandria N, El-Himri Rawan K, Chapa Valerie A, Tan Lin, Tran Bao Q, Pham Dung, Halsey Taylor M, Jin Yimei, Tsai Wen-Bin, Prasad Rishika, Glover Israel K, Ajami Nadim J, Wargo Jennifer A, Shelburne Samuel, Okhuysen Pablo C, Liu Chen, Fowler Stephanie W, Conner Margaret E, Peterson Christine B, Rondon Gabriela, Molldrem Jeffrey J, Champlin Richard E, Shpall Elizabeth J, Lorenzi Philip L, Mehta Rohtesh S, Martens Eric C, Alousi Amin M, Jenq Robert R

机构信息

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Res Sq. 2023 Jan 31:rs.3.rs-2460097. doi: 10.21203/rs.3.rs-2460097/v1.

DOI:10.21203/rs.3.rs-2460097/v1

PMID:36778495

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9915792/

Abstract

Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing reduced severity of GVHD and improved survival. reduced degradation of colonic mucus by another intestinal commensal, , via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by and reduce GVHD-related mortality.

摘要

急性胃肠道移植物抗宿主病（aGI-GVHD）是异基因造血干细胞移植的一种严重并发症，已知肠道微生物群会影响其严重程度。然而，aGI-GVHD的治疗反应与肠道微生物群之间的关联尚未得到充分研究。在一组aGI-GVHD患者（n=37）中，我们发现对皮质类固醇标准治疗无反应与先前使用碳青霉烯类抗生素治疗以及微生物群中[具体微生物名称缺失]的丧失有关。在碳青霉烯类加重GVHD的小鼠模型中，引入[具体微生物名称缺失]可降低GVHD的严重程度并提高生存率。[具体微生物名称缺失]通过其将膳食多糖代谢为单糖的能力，减少了另一种肠道共生菌[具体微生物名称缺失]对结肠黏液的降解，进而抑制[具体微生物名称缺失]对黏液的降解并降低GVHD相关死亡率。