Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway
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...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2488105 |
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| author | Yang Jiao Jiawei Ren Shichang Xie Nan Yuan Jiaqi Shen Huafang Yin Jian Wang Hongjuan Guo Jianping Cao Xin Wang Depei Wu Zhemin Zhou Xiaofei Qi |
| author_facet | Yang Jiao Jiawei Ren Shichang Xie Nan Yuan Jiaqi Shen Huafang Yin Jian Wang Hongjuan Guo Jianping Cao Xin Wang Depei Wu Zhemin Zhou Xiaofei Qi |
| author_sort | Yang Jiao |
| collection | DOAJ |
| description | 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-κB-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. |
| format | Article |
| id | doaj-art-af3e8a73dbee48f9a2da594898ee9408 |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-af3e8a73dbee48f9a2da594898ee94082025-08-20T02:08:12ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2488105Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathwayYang Jiao0Jiawei Ren1Shichang Xie2Nan Yuan3Jiaqi Shen4Huafang Yin5Jian Wang6Hongjuan Guo7Jianping Cao8Xin Wang9Depei Wu10Zhemin Zhou11Xiaofei Qi12State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaKey Laboratory of Alkene-Carbon Fibers-Based Technology & Application for Detection of Major Infectious Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Cancer Institute, Suzhou Medical College, Soochow University, Suzhou, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaThe Affiliated Jiangyin People’s Hospital of Nantong University, Jiangyin, ChinaThe Affiliated Jiangyin People’s Hospital of Nantong University, Jiangyin, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products & Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou, ChinaState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaKey Laboratory of Alkene-Carbon Fibers-Based Technology & Application for Detection of Major Infectious Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Cancer Institute, Suzhou Medical College, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou, ChinaRadiation-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-κB-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.https://www.tandfonline.com/doi/10.1080/19490976.2025.2488105Radiation-induced hematopoietic injurygut microbiomeBacteroides acidifaciensraffinose-metabolizing bacteriaIntestinal-Hematopoietic AxisUDCA |
| spellingShingle | Yang Jiao Jiawei Ren Shichang Xie Nan Yuan Jiaqi Shen Huafang Yin Jian Wang Hongjuan Guo Jianping Cao Xin Wang Depei Wu Zhemin Zhou Xiaofei Qi Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway Gut Microbes Radiation-induced hematopoietic injury gut microbiome Bacteroides acidifaciens raffinose-metabolizing bacteria Intestinal-Hematopoietic Axis UDCA |
| title | Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway |
| title_full | Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway |
| title_fullStr | Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway |
| title_full_unstemmed | Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway |
| title_short | Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway |
| title_sort | raffinose metabolizing bacteria impair radiation associated hematopoietic recovery via the bile acid fxr nf κb signaling pathway |
| topic | Radiation-induced hematopoietic injury gut microbiome Bacteroides acidifaciens raffinose-metabolizing bacteria Intestinal-Hematopoietic Axis UDCA |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2488105 |
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