Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway
文献类型： 外文期刊
第一作者： Jiao, Yang
作者： Jiao, Yang;Ren, Jiawei;Yuan, Nan;Shen, Jiaqi;Guo, Hongjuan;Cao, Jianping;Wu, Depei;Jiao, Yang;Ren, Jiawei;Yuan, Nan;Guo, Hongjuan;Cao, Jianping;Jiao, Yang;Wu, Depei;Qi, Xiaofei;Xie, Shichang;Zhou, Zhemin;Shen, Jiaqi;Wu, Depei;Qi, Xiaofei;Shen, Jiaqi;Wu, Depei;Qi, Xiaofei;Shen, Jiaqi;Wu, Depei;Yin, Huafang;Wang, Jian;Wang, Xin;Wang, Xin;Zhou, Zhemin;Zhou, Zhemin
作者机构：
关键词：
Radiation-induced hematopoietic injury; gut microbiome;
期刊名称：GUT MICROBES （ 影响因子：11.0； 五年影响因子：13.4 ）
ISSN： 1949-0976
年卷期： 2025 年 17 卷 1 期
页码：
收录情况： SCI
摘要： Radiation-associated hematopoietic recovery (RAHR) is critical for mitigating lethal complications of acute radiation syndrome (ARS), yet therapeutic strategies remain limited. Through integrated multi-omics analysis of a total body irradiation (TBI) mouse model, we identify Bacteroides acidifaciens-dominated gut microbiota as key mediators of RAHR impairment. 16S ribosomal rRNA sequencing revealed TBI-induced dysbiosis characterized by Bacteroidaceae enrichment, while functional metagenomics identified raffinose metabolism as the most significantly perturbed pathway. Notably, raffinose supplementation (10% w/v) recapitulated radiation-induced microbiota shifts and delayed bone marrow recovery. Fecal microbiota transplantation (FMT) revealed a causative role for raffinose-metabolizing microbiota, particularly Bacteroides acidifaciens, in delaying RAHR progression. Mechanistically, B. acidifaciens-mediated bile acid deconjugation activated FXR, subsequently suppressing NF-kappa B-dependent hematopoietic recovery. Therapeutic FXR inhibition via ursodeoxycholic acid (UDCA) had been shown to be a viable method for rescuing RAHR. Our results delineated a microbiome-bile acid-FXR axis as a master regulator of post-irradiation hematopoiesis. Targeting B. acidifaciens or its metabolic derivatives could represent a translatable strategy to mitigate radiation-induced hematopoietic injury.
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