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Disrupted gut microecology after high-dose 131I therapy and radioprotective effects of arachidonic acid supplementation.
Lu, Ganghua; Gao, Dingwei; Jiang, Wen; Yu, Xiaqing; Tong, Junyu; Liu, Xiaoyan; Qiao, Tingting; Wang, Ru; Zhang, Mengyu; Wang, Shaoping; Yang, Jianshe; Li, Dan; Lv, Zhongwei.
Afiliación
  • Lu G; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Gao D; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Jiang W; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Yu X; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Tong J; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Liu X; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Qiao T; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Wang R; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Zhang M; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Wang S; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  • Yang J; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China. yangjs@impcas.ac.cn.
  • Li D; Department of Nuclear Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510289, China. lidan269@mail.sysu.edu.cn.
  • Lv Z; Clinical Nuclear Medicine Center, Imaging Clinical Medical Center, Institute of Nuclear Medicine, Department of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China. Lvzwjs2020@163.com.
Eur J Nucl Med Mol Imaging ; 51(8): 2395-2408, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38561516
ABSTRACT

BACKGROUND:

Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment.

METHODS:

A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses.

RESULTS:

131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1.

CONCLUSION:

These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Protectores contra Radiación / Ácido Araquidónico / Microbioma Gastrointestinal / Radioisótopos de Yodo Idioma: En Revista: Eur J Nucl Med Mol Imaging Año: 2024 Tipo del documento: Article País de afiliación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Protectores contra Radiación / Ácido Araquidónico / Microbioma Gastrointestinal / Radioisótopos de Yodo Idioma: En Revista: Eur J Nucl Med Mol Imaging Año: 2024 Tipo del documento: Article País de afiliación: China