Disrupted gut microecology after high-dose <sup>131</sup>I therapy and radioprotective effects of arachidonic acid supplementation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38561516.
- Also identified by DOI 10.1007/s00259-024-06688-9 and PMC identifier 11178657.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose <sup>131</sup>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 <sup>131</sup>I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. A total of 102 patients with DTC were recruited, with fecal samples collected before and after <sup>131</sup>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. <sup>131</sup>I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after <sup>131</sup>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. 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.
Medical subject headings
- Gastrointestinal Microbiome
- Iodine Radioisotopes
- Radiation-Protective Agents
- Arachidonic Acid