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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

作者: Jiao, Yang 1 ; Ren, Jiawei 1 ; Xie, Shichang 4 ; Yuan, Nan 1 ; Shen, Jiaqi 1 ; Yin, Huafang 8 ; Wang, Jian 8 ; Guo, Hongjuan 1 ; Cao, Jianping 1 ; Wang, Xin 9 ; Wu, Depei 1 ; Zhou, Zhemin 4 ; Qi, Xiaofei 3 ;

作者机构: 1.Soochow Univ, Sch Radiat Med & Protect, State Key Lab Radiat Med & Protect, Suzhou, Peoples R China

2.Soochow Univ, Jiangsu Higher Educ Inst, Collaborat Innovat Ctr Radiol Med, Suzhou, Peoples R China

3.Jiangsu Inst Hematol, Natl Clin Res Ctr Hematol Dis, Collaborat Innovat Ctr Hematol, Suzhou, Peoples R China

4.Soochow Univ, Canc Inst, Key Lab Alkene Carbon Fibers Based Technol & Appli, MOE Key Lab Geriatr Dis & Immunol,Suzhou Med Coll, Suzhou, Peoples R China

5.Soochow Univ, Affiliated Hosp 1, Dept Hematol, 188 Shizi St, Suzhou 215006, Peoples R China

6.Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou, Peoples R China

7.Soochow Univ, Inst Blood & Marrow Transplantat, Suzhou, Peoples R China

8.Nantong Univ, Affiliated Jiangyin Peoples Hosp, Jiangyin, Peoples R China

9.Zhejiang Acad Agr Sci, State Key Lab Managing Biot & Chem Threats Qual &, Hangzhou, Peoples R China

10.Zhejiang Acad Agr Sci, Inst Food Sci, Hangzhou, Peoples R China

11.Soochow Univ, Affiliated Hosp 2, Canc Inst, Suzhou Med Coll, Suzhou, Peoples R China

12.Suzhou Biomed Ind Innovat Ctr, Natl Ctr Technol Innovat Biopharmaceut, Suzhou, Peoples R China

关键词: Radiation-induced hematopoietic injury; gut microbiome; Bacteroides acidifaciens; raffinose-metabolizing bacteria; Intestinal-Hematopoietic Axis; UDCA; FXR

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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