Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease,Cell Host & Microbe

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Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-08-29 , DOI: 10.1016/j.chom.2024.08.004
Eiko Hayase ₁ , Tomo Hayase ₁ , Akash Mukherjee ₂ , Stuart C Stinson ₂ , Mohamed A Jamal ₁ , Miriam R Ortega ₁ , Christopher A Sanchez ₁ , Saira S Ahmed ₁ , Jennifer L Karmouch ₁ , Chia-Chi Chang ₁ , Ivonne I Flores ₁ , Lauren K McDaniel ₁ , Alexandria N Brown ₁ , Rawan K El-Himri ₁ , Valerie A Chapa ₁ , Lin Tan ₃ , Bao Q Tran ₃ , Yao Xiao ₄ , Christopher Fan ₁ , Dung Pham ₁ , Taylor M Halsey ₁ , Yimei Jin ₁ , Wen-Bin Tsai ₁ , Rishika Prasad ₁ , Israel K Glover ₁ , Altai Enkhbayar ₁ , Aqsa Mohammed ₁ , Maren Schmiester ₁ , Katherine Y King ₅ , Robert A Britton ₆ , Pavan Reddy ₇ , Matthew C Wong ₁ , Nadim J Ajami ₁ , Jennifer A Wargo ₁ , Samuel Shelburne ₈ , Pablo C Okhuysen ₉ , Chen Liu ₁₀ , Stephanie W Fowler ₁₁ , Margaret E Conner ₁₂ , Zoe Katsamakis ₁₃ , Natalie Smith ₁₃ , Marina Burgos da Silva ₁₃ , Doris M Ponce ₁₃ , Jonathan U Peled ₁₄ , Marcel R M van den Brink ₁₄ , Christine B Peterson ₁₅ , Gabriela Rondon ₂ , Jeffrey J Molldrem ₁₆ , Richard E Champlin ₂ , Elizabeth J Shpall ₂ , Philip L Lorenzi ₃ , Rohtesh S Mehta ₂ , Eric C Martens ₄ , Amin M Alousi ₂ , Robert R Jenq ₁₇

Affiliation

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Center for Cell and Gene Therapy and Department of Pediatrics, Division of Infectious Diseases, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
Department of Molecular Virology and Microbiology and Department of Education, Innovation, and Technology, Baylor College of Medicine, Houston, TX 77030, USA; Center for Comparative Medicine and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Molecular Virology and Microbiology and Department of Education, Innovation, and Technology, Baylor College of Medicine, Houston, TX 77030, USA.
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10021, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Hematopoietic Biology & Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; CPRIT Scholar in Cancer Research, Houston, TX, USA.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.

中文翻译：

卵形拟杆菌减轻了菌群失调诱导的移植物抗宿主病

急性下消化道 GVHD （aLGI-GVHD）是同种异体造血干细胞移植的严重并发症。尽管肠道菌群与 aLGI-GVHD 的发病率相关，但肠道菌群如何影响 aLGI-GVHD 的治疗反应尚未得到彻底研究。在 aLGI-GVHD 患者队列（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和以卵形拟杆菌丰度降低为特征的粪便微生物组破坏有关。在碳青霉烯类抗生素加重的小鼠 GVHD 模型中，引入卵形芽孢杆菌可降低 GVHD 的严重程度并提高生存率。卵形拟杆菌的这些有益作用与其将膳食多糖代谢成单糖的能力有关，单糖抑制了结肠粘液降解剂（如拟杆菌 thetaiotaomicron 和嗜粘蛋白阿克曼菌）的粘液降解能力，从而降低了 GVHD 相关的死亡率。总的来说，这些发现揭示了微生物群在 aLGI-GVHD 中的重要性以及卵形芽孢杆菌的治疗潜力。

更新日期：2024-08-29

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