| RRC ID |
88795
|
| 著者 |
Jiao Y, Ren J, Xie S, Yuan N, Shen J, Yin H, Wang J, Guo H, Cao J, Wang X, Wu D, Zhou Z, Qi X.
|
| タイトル |
Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway.
|
| ジャーナル |
Gut Microbes
|
| Abstract |
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.
|
| 巻・号 |
17(1)
|
| ページ |
2488105
|
| 公開日 |
2025-12-1
|
| DOI |
10.1080/19490976.2025.2488105
|
| PMID |
40192235
|
| PMC |
PMC11980471
|
| MeSH |
Acute Radiation Syndrome* / metabolism
Acute Radiation Syndrome* / microbiology
Animals
Bacteria* / classification
Bacteria* / genetics
Bacteria* / isolation & purification
Bacteria* / metabolism
Bile Acids and Salts* / metabolism
Dysbiosis / microbiology
Fecal Microbiota Transplantation
Gastrointestinal Microbiome* / radiation effects
Hematopoiesis* / radiation effects
Male
Mice
Mice, Inbred C57BL
NF-kappa B* / genetics
NF-kappa B* / metabolism
Raffinose* / metabolism
Receptors, Cytoplasmic and Nuclear* / genetics
Receptors, Cytoplasmic and Nuclear* / metabolism
Signal Transduction / radiation effects
Whole-Body Irradiation / adverse effects
|
| リソース情報 |
| 一般微生物 |
JCM10556 |
