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

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.

Body composition changes in patients with differentiated thyroid cancer after iodine-131 treatment and short-term levothyroxine replacement and suppression therapy.

PURPOSE: The purposes of this study were to assess the changes in body composition in patients who underwent thyroidectomy due to differentiated thyroid cancer (DTC) after radioactive iodine therapy (RAI) and short-term levothyroxine (LT4) supplementation and to explore the correlations between body composition distribution and corresponding blood indices. METHODS: Fifty-seven thyroidectomized DTC patients were included. Serum was tested for several biochemical indices of thyroid function, lipids, and bone metabolism, and body composition parameters were measured via dual-energy X-ray absorptiometry before and 4-6 weeks after RAI and LT4 supplementation. RESULTS: The body composition of DTC patients changed after RAI. Fat mass in all parts of the body decreased (range of relative change (RRC) -12.97--2.80%). Bone mineral content (BMC) increased throughout the body (relative change (RC) 12.12%), head (RC 36.23%), pelvis (RC 9.00%), and legs (RC 3.15%). Similarly, bone mineral density (BMD) increased in different regions (RRC 3.60-26.43%), except for the arms. Notably, lean mass in the arms (RC 4.30%) and legs (RC 3.67%) increased, while that in the head decreased (RC -2.75%), while total lean mass did not change at 4-6 weeks after LT4 supplementation. Furthermore, changes in fat distribution in the android region were related to the changes in total cholesterol (r = -0.390) and low-density lipoprotein cholesterol (r = -0.354), and changes in the BMC and BMD of the lumbar spine were positively associated with the changes in calcitonin (r = 0.302 and 0.325, respectively). CONCLUSIONS: After RAI and short-term LT4 supplementation in DTC patients, body composition rapidly and positively changed and was characterized by decreased fat mass and increased BMC and BMD.

Insight Into Mouse Models of Hyperthyroidism.

Hyperthyroidism is characterized by an increase in the synthesis and secretion of thyroid hormones in the thyroid gland, and the most common cause of overproduction of thyroid hormones is Graves' disease (GD). Long-term disease models of hyperthyroidism have been established. In general, methods to induce GD include transfection of fibroblasts, injecting plasmids or adenovirus containing thyroid stimulating hormone receptor (TSHR) or TSHR subunit, and exogenous artificial thyroid hormone supplementation. Fortunately, in mouse studies, novel treatments for GD and Graves' orbitopathy (GO) were discovered. It has been reported that prophylactic administration of TSHR A subunit protein in genetically susceptible individuals could induce immune tolerance and provide protection for the future development of GD. Biologically active monoclonal antibody against intracellular adhesion molecule-1 (ICAM-1 mAb) and siRNA targeting TSHR can also be used to treat GD. Moreover, new potential therapeutic targets have been identified in GO mouse models, and these targets could present novel therapeutic approaches. Besides, human placental mesenchymal stem cells (hPMSCs) into the orbit, fucoxanthin and icariin may be new alternative therapies that could be used in addition to the existing drugs, although further research is needed.