1. 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.
- Author
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Han, Lijie, Sun, Xianlei, Kong, Jingjing, Li, Jin, Feng, Kai, Bai, Yanliang, Wang, Xianjing, Zhu, Zhenhua, Yang, Fengyuan, Chen, Qingzhou, Zhang, Mengmeng, Yue, Baohong, Wang, Xiaoqian, Fu, Liyan, Chen, Yaoyao, Yang, Qiankun, Wang, Shuya, Xin, Qingxuan, Sun, Nannan, and Zhang, Danfeng
- Subjects
HEMATOPOIETIC stem cell transplantation ,GRAFT versus host disease ,BILE acids ,GUT microbiome ,T cells - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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