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Tytuł pozycji:

Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein.

Tytuł :
Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein.
Autorzy :
Xiao HW; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China.
Cui M; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China. .
Li Y; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China.
Dong JL; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China.
Zhang SQ; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China.
Zhu CC; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China.
Jiang M; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China.
Zhu T; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China.
Wang B; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China.
Wang HC; Laboratory of Emergency Medicine, Feinstein Institute for Medical Research, Manhasset, NY, USA.
Fan SJ; Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China. .
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Źródło :
Microbiome [Microbiome] 2020 May 20; Vol. 8 (1), pp. 69. Date of Electronic Publication: 2020 May 20.
Typ publikacji :
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
Język :
English
Imprint Name(s) :
Original Publication: London: BioMed Central, 2013-
MeSH Terms :
Diazepam Binding Inhibitor*/metabolism
Fecal Microbiota Transplantation*
Gastrointestinal Microbiome*/drug effects
Gastrointestinal Microbiome*/radiation effects
Indoles*/administration & dosage
Indoles*/pharmacology
Radiation Injuries*/therapy
Animals ; Cell Line ; Feces/chemistry ; Female ; Gastrointestinal Tract/drug effects ; Gastrointestinal Tract/microbiology ; Hematopoiesis/drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Pregnane X Receptor/metabolism ; RNA, Ribosomal, 16S/genetics ; Signal Transduction/drug effects
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Grant Information :
R01 AT005076 United States AT NCCIH NIH HHS; R01 GM063075 United States GM NIGMS NIH HHS; P30 CA196521 United States CA NCI NIH HHS; OCM-094 International Centers for Medicare and Medicaid Services
Contributed Indexing :
Keywords: ACBP*; Acute radiation syndrome*; Gastrointestinal tract toxicity*; Gut microbiota*; Gut microbiota metabolite*; Hematopoietic toxicity*; Indole 3-propionic acid*; Radiotherapy*
Substance Nomenclature :
0 (Diazepam Binding Inhibitor)
0 (Indoles)
0 (Pregnane X Receptor)
0 (RNA, Ribosomal, 16S)
830-96-6 (indolepropionic acid)
Entry Date(s) :
Date Created: 20200522 Date Completed: 20210301 Latest Revision: 20210301
Update Code :
20210309
PubMed Central ID :
PMC7241002
DOI :
10.1186/s40168-020-00845-6
PMID :
32434586
Czasopismo naukowe
Background: We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely characterized. Here, we aimed to tease apart the gut microbiota-produced metabolites, underpin the therapeutic effects of FMT to radiation injuries, and elucidate the underlying molecular mechanisms.
Results: FMT elevated the level of microbial-derived indole 3-propionic acid (IPA) in fecal pellets from irradiated mice. IPA replenishment via oral route attenuated hematopoietic system and gastrointestinal (GI) tract injuries intertwined with radiation exposure without precipitating tumor growth in male and female mice. Specifically, IPA-treated mice represented a lower system inflammatory level, recuperative hematogenic organs, catabatic myelosuppression, improved GI function, and epithelial integrity following irradiation. 16S rRNA gene sequencing and subsequent analyses showed that irradiated mice harbored a disordered enteric bacterial pattern, which was preserved after IPA administration. Notably, iTRAQ analysis presented that IPA replenishment retained radiation-reprogrammed protein expression profile in the small intestine. Importantly, shRNA interference and hydrodynamic-based gene delivery assays further validated that pregnane X receptor (PXR)/acyl-CoA-binding protein (ACBP) signaling played pivotal roles in IPA-favored radioprotection in vitro and in vivo.
Conclusions: These evidences highlight that IPA is a key intestinal microbiota metabolite corroborating the therapeutic effects of FMT to radiation toxicity. Owing to the potential pitfalls of FMT, IPA might be employed as a safe and effective succedaneum to fight against accidental or iatrogenic ionizing ARS in clinical settings. Our findings also provide a novel insight into microbiome-based remedies toward radioactive diseases. Video abstract.

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