Sexual Dimorphism of Gut Microbiota Dictates Therapeutics Efficacy of Radiation Injuries

Abstract: Accidental or iatrogenic ionizing radiation exposure precipitates acute and chronic radiation injuries. The traditional paradigm of mitigating radiotherapy‐associated adverse side effects has ignored the gender‐specific dimorphism of patients' divergent responses. Here, the effects of sexual dimorphism on curative efficiencies of therapeutic agents is examined in murine models of irradiation injury. Oral gavage of simvastatin ameliorates radiation‐induced hematopoietic injury and gastrointestinal tract dysfunction in male mice, but adversely deteriorates these radiation syndromes in female animals. In a sharp contrast, feeding animals with high‐fat diet (HFD) elicites explicitly contrary results. High‐throughput sequencing of microbial 16S rRNA, host miRNA, and mRNA shows that simvastatin or HFD administration preventes radiation‐altered enteric bacterial taxonomic structure, preserves miRNA expression profile, and reprogrammes the spectrum of mRNA expression in small intestines of male or female mice, respectively. Notably, faecal microbiota transplantation of gut microbes from opposite sexual donors abrogates the curative effects of simvastatin or HFD in respective genders of animals. Together, these findings demonstrate that curative efficiencies of therapeutic strategies mitigating radiation toxicity might be dependent on the gender of patients, thus simvastatin or HFD might be specifically useful for fighting against radiation toxicity in a sex‐dependent fashion partly based on sex‐distinct gut microbiota composition in preclinical settings.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Sexual Dimorphism of Gut Microbiota Dictates Therapeutics Efficacy of Radiation Injuries ; volume:6 ; number:21 ; year:2019 ; extent:13
Advanced science ; 6, Heft 21 (2019) (gesamt 13)

Creator
Cui, Ming
Xiao, Huiwen
Li, Yuan
Zhang, Shuqin
Dong, Jiali
Wang, Bin
Zhu, Changchun
Jiang, Mian
Zhu, Tong
He, Junbo
Wang, Haichao
Fan, Saijun

DOI
10.1002/advs.201901048
URN
urn:nbn:de:101:1-2022072506504706502689
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:32 AM CEST

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Associated

  • Cui, Ming
  • Xiao, Huiwen
  • Li, Yuan
  • Zhang, Shuqin
  • Dong, Jiali
  • Wang, Bin
  • Zhu, Changchun
  • Jiang, Mian
  • Zhu, Tong
  • He, Junbo
  • Wang, Haichao
  • Fan, Saijun

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