Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway

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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gut Microbes
Subjects:
Radiation-induced hematopoietic injury
gut microbiome
Bacteroides acidifaciens
raffinose-metabolizing bacteria
Intestinal-Hematopoietic Axis
UDCA
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2025.2488105
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1949-0976
1949-0984

Similar Items