Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism

Autor: Lijie Han, Xianlei Sun, Jingjing Kong, Jin Li, Kai Feng, Yanliang Bai, Xianjing Wang, Zhenhua Zhu, Fengyuan Yang, Qingzhou Chen, Mengmeng Zhang, Baohong Yue, Xiaoqian Wang, Liyan Fu, Yaoyao Chen, Qiankun Yang, Shuya Wang, Qingxuan Xin, Nannan Sun, Danfeng Zhang, Yiwei Zhou, Yanxia Gao, Junwei Zhao, Yong Jiang, Rongqun Guo
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Translational Medicine, Vol 22, Iss 1, Pp 1-24 (2024)
Druh dokumentu: article
ISSN: 1479-5876
DOI: 10.1186/s12967-024-05577-x
Popis: Abstract Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving “immune cell-gut microbes-bile acid metabolites” contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD. Graphical abstract
Databáze: Directory of Open Access Journals
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