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Disrupted gut microecology after high-dose 131I therapy and radioprotective effects of arachidonic acid supplementation.

Authors :
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
Source :
European Journal of Nuclear Medicine & Molecular Imaging; Jul2024, Vol. 51 Issue 8, p2395-2408, 14p
Publication Year :
2024

Abstract

Background: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose <superscript>131</superscript>I 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 <superscript>131</superscript>I 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 <superscript>131</superscript>I 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: <superscript>131</superscript>I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after <superscript>131</superscript>I 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16197070
Volume :
51
Issue :
8
Database :
Complementary Index
Journal :
European Journal of Nuclear Medicine & Molecular Imaging
Publication Type :
Academic Journal
Accession number :
177896457
Full Text :
https://doi.org/10.1007/s00259-024-06688-9