Early and long-term responses of intestinal microbiota and metabolites to 131I treatment in differentiated thyroid cancer patients.

BACKGROUND: Multiple high doses of 131I therapy in patients with differentiated thyroid cancer (DTC) might disrupt the balance of gut microbiota and metabolites. This study aimed to investigate the alterations of intestinal bacteria and metabolism over two courses of 131I therapy, explore the interactions, and construct diagnostic models reflecting enteric microecology based on 131I therapy. METHODS: A total of 81 patients were recruited for the first 131I therapy (131I-1st), among whom 16 received a second course (131I-2nd) after half a year. Fecal samples were collected 1 day before (Pre-131I-1st/2nd) and 3 days after (Post-131I-1st/2nd) 131I therapy for microbiome (16S rRNA gene sequencing) and metabolomic (LC-MS/MS) analyses. RESULTS: A total of six microbial genera and 11 fecal metabolites enriched in three pathways were identified to show significant differences between Pre-131I-1st and other groups throughout the two courses of 131I treatment. In the Post-131I-1st group, the beneficial bacteria Bifidobacterium, Lachnoclostridium, uncultured_bacterium_f_Lachnospiraceae, and Lachnospiraceae_UCG004 were abundant and the radiation-sensitive pathways of linoleic acid (LA), arachidonic acid, and tryptophan metabolism were inhibited compared with the Pre-131I-1st group. Compared with the Pre-131I-1st group, the Pre-131I-2nd group exhibited a reduced diversity of flora and differentially expressed metabolites, with a low abundance of beneficial bacteria and dysregulated radiation-sensitive pathways. However, less significant differences in microbiota and metabolites were found between the Pre/Post-131I-2nd groups compared with those between the Pre/Post-131I-1st groups. A complex co-occurrence was observed between 6 genera and 11 metabolites, with Lachnoclostridium, Lachnospiraceae_UCG004, Escherichia-Shigella, and LA-related metabolites contributing the most. Furthermore, combined diagnostic models of charactered bacteria and metabolites answered well in the early, long-term, and dose-dependent responses for 131I therapy. CONCLUSIONS: Different stages of 131I therapy exert various effects on gut microecology, which play an essential role in regulating radiotoxicity and predicting the therapeutic response.

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.

The Potential Role of Pyrroloquinoline Quinone to Regulate Thyroid Function and Gut Microbiota Composition of Graves' Disease in Mice.

Graves' disease (GD) is an autoimmune disorder disease, and its prevalence continues to increase worldwide. Pyrroloquinoline quinone (PQQ) is a naturally antioxidant compound in milk, vegetables, and meat. We aim to identify the treatment efficacy of PQQ on GD and its regulatory effect on intestinal microbiota. The GD mice model was built by an adenovirus expressing autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). Fecal samples were collected for 16S rDNA sequencing after PQQ pretreatments (20, 40, or 60 mg/kg BW/day) for 4 weeks. Thyroid and intestine functions were measured. The levels of serum TSHR and T4 were significantly raised, and the thyroid gland size was typically enlarged in the GD group than in controls, reversed by PQQ therapy. After PQQ replenishment, IL6 and TNFα levels in small intestine tissues were lower than those in the GD group, with Nrf2 and HO1 levels improved. Also, the PQQ supplement could maintain the mucosal epithelial barrier impaired by GD. In microbial analyses, PQQ treatment could prompt the diversity recovery of gut microbiota and reconstruct the microbiota composition injured by GD. Lactobacillus served as the most abundant genus in all groups, and the abundance of Lactobacillus was increased in the GD group than in control and PQQ groups. Besides, Lactobacillus was highly correlative with all samples and the top 50 genera. PQQ supplementation regulates thyroid function and relieves intestine injury. PQQ changes the primary composition and abundance of GD's intestine microbiota by moderating Lactobacillus, which may exert in the pathogenesis and progression of GD.

Integrated microbiome and metabolome analysis reveals a distinct microbial and metabolic signature in Graves' disease and hypothyroidism.

Recent studies reveal that imbalanced microbiota is related to thyroid diseases. However, studies on the alterations in fecal metabolites in Graves' disease and clinical hypothyroidism patients are insufficient. Here, we identified 21 genera and 53 metabolites that were statistically significant among Graves' disease patients, hypothyroidism patients, and controls integrating microbiome and untargeted metabolome analysis. Disease groups revealed a decreased abundance in butyrate-producing microbiota and an increased abundance in potentially pathogenic microbiota. Lipids molecules were the major differential metabolites identified in all fecal samples. Network analysis recognized that microbiota may affect thyroid function by targeting specific metabolites. We further identified specific microbiota and metabolites that could distinguish Graves' disease patients, hypothyroidism patients, and controls. Our study reveals a distinct microbial and metabolic signature in hypothyroidism patients and Graves' disease patients and further validates the potential role of microbiota in thyroid diseases, providing new ideas for future research into the etiology and clinical intervention of thyroid diseases.

Effect of low-dose radiation on thyroid function and the gut microbiota.

BACKGROUND: The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition. AIM: To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice. METHODS: Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation. RESULTS: We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair. CONCLUSION: LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose.

Evaluation and analysis of anxiety and depression symptoms for college students during COVID-19 pandemic.

BACKGROUND: The mental health of students is affected by COVID-19. We aim to evaluate the anxiety and depression symptoms among college students during COVID-19 pandemic, analyze the influence factors that contribute to college students' anxiety and depression symptoms, and provide some suggestions for improving the mental health of college students. METHODS: With 179 college students participating, an online questionnaire consisting of a general questionnaire, Generalized Anxiety Disorder (GAD-7), and Patient Health Questionnaire (PHQ-9) was conducted in universities in Shanghai. The anxiety and depression symptoms among college students were evaluated using GAD-7 and PHQ-9 scales, and influence factors were analyzed using an unordered multi-class Logistic regression model. RESULTS: The reliability and validity of the GAD-7 and PHQ-9 scales were good (reliability ≥ 0.9, validity = 100%). The incidence of anxiety was 32.4%, of which were 23.5%, 8.4%, and 0.6% in mild, moderate, and severe, respectively; and the incidence of depression was 46.40%, of which in mild, moderate, moderate to severe, and severe were 28.5%, 10.1%, 7.3%, and 0.6%, respectively. Multivariate analysis revealed that male students with strong psychological quality, who were not easily affected by the COVID-19 pandemic, who received less negative or false information, and who had a strong grasp of psychology and related knowledge were less likely to suffer from mild or moderate anxiety symptoms [OR (95% CI) 0.18 (0.04, 0.81), 0.12 (0.05, 0.33), 0.23 (0.06, 0.89) and 0.07 (0.01, 0.74)]. Furthermore, college students who were not affected by the COVID-19 pandemic were less likely to suffer from mild, moderate, and moderate to severe depression symptoms [OR (95% CI) 0.23 (0.08, 0.65), 0.22 (0.05, 0.93), 0.10 (0.02, 0.54)]. CONCLUSION: The GAD-7 and PHQ-9 scales are suitable for evaluating anxiety and depression symptoms in college students. The COVID-19 pandemic was associated with a high incidence of anxiety and depression symptoms among college students, although gender and mental state fluctuations during the pandemic, negative and false information, and exposure to psychology and related courses were the main influencing factors.

The relationships between the gut microbiota and its metabolites with thyroid diseases.

Emerging studies have provided a preliminary understanding of the thyroid-gut axis, indicating that intestinal microbiota and its metabolites may act directly or indirectly on the thyroid by influencing intestinal microelements uptake, iodothyronine conversion and storage, and immune regulation, providing new insights into the pathogenesis of thyroid disorders and clinical management strategies. However, the research on gut microbiota and thyroid has only presented the tip of the iceberg. More robust clinical data and basic experiments are still required to elucidate the specific relationships and mechanisms in the future. Here we will characterize the associations between the microbiota and thyroid diseases to evaluate their potential implications in the pathophysiology and open up scientific avenues for future precision studies of the thyroid-gut axis.

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.

Alterations of Gut Microbiome and Metabolite Profiles Associated With Anabatic Lipid Dysmetabolism in Thyroid Cancer.

Background: Currently, the high morbidity of individuals with thyroid cancer (TC) is an increasing health care burden worldwide. The aim of our study was to investigate the relationship among the gut microbiota community, metabolites, and the development of differentiated thyroid cancer. Methods: 16S rRNA gene sequencing and an integrated LC-MS-based metabolomics approach were performed to obtain the components and characteristics of fecal microbiota and metabolites from 50 patients with TC and 58 healthy controls (HCs). Results: The diversity and richness of the gut microbiota in the TC patients were markedly decreased. The composition of the gut microbiota was significantly altered, and the Bacteroides enterotype was the dominant enterotype in TC patients. Additionally, the diagnostic validity of the combined model (three genera and eight metabolites) and the metabolite model (six metabolites) were markedly higher than that of the microbial model (seven genera) for distinguishing TC patients from HCs. LEfSe analysis demonstrated that genera (g_Christensenellaceae_R-7_group, g_Eubacterium_coprostanoligenes_group) and metabolites [27-hydroxycholesterol (27HC), cholesterol] closely related to lipid metabolism were greatly reduced in the TC group. In addition, a clinical serum indicator (total cholesterol) and metabolites (27HC and cholesterol) had the strongest influence on the sample distribution. Furthermore, functional pathways related to steroid biosynthesis and lipid digestion were inhibited in the TC group. In the microbiota-metabolite network, 27HC was significantly related to metabolism-related microorganisms (g_Christensenellaceae_R-7_group). Conclusions: Our research explored the characteristics of the gut microecology of patients with TC. The findings of this study will help to discover risk factors that affect the occurrence and development of TC in the intestinal microecology.

Effectiveness of mobile robots collecting vital signs and radiation dose rate for patients receiving Iodine-131 radiotherapy: A randomized clinical trial.

Objective: Patients receiving radionuclide 131I treatment expose radiation to others, and there was no clinical trial to verify the effectiveness and safety of mobile robots in radionuclide 131I isolation wards. The objective of this randomized clinical trial was to evaluate the effectiveness and safety of mobile robots in providing vital signs (body temperature and blood pressure) and radiation dose rate monitoring for patients receiving radionuclide therapy. Methods: An open-label, multicenter, paired, randomized clinical trial was performed at three medical centers in Shanghai and Wuhan, China, from 1 April 2018 to 1 September 2018. A total of 72 participants were assigned to the group in which vital signs and radiation doses were both measured by mobile robots and conventional instruments. Intergroup consistency, completion rate, and first success rate were the primary effectiveness measures, and vital sign measurement results, the error rate of use, and subjective satisfaction were secondary indicators. Adverse events related to the robot were used to assess safety. Results: Of the 72 randomized participants (median age, 39.5; 27 [37.5%] male participants), 72 (100.0%) completed the trial. The analysis sets of full analysis set, per-protocol set, and safety analysis set included 72 cases (32 cases in Center A, 16 cases in Center B, and 24 cases in Center C). The consistency, completion rate, and first success rate were 100% (P = 1.00), and the first success rates of vital signs and radiation dose rate were 91.7% (P = 1.000), 100.0% (P = 0.120), and 100.0% (P = 1.000). There was no significant difference in vital signs and radiation dose rate measurement results between the robot measurement group and the control group (P = 0.000, 0.044, and 0.023), and subjective satisfaction in the robot measurement group was 71/72 (98.6%), compared to 67/72 (93.1%) in the control group. For safety evaluation, there was no adverse event related to the mobile robot. Conclusion: The mobile robots have good effectiveness and safety in providing vital signs and radiation dose rate measurement services for patients treated with radionuclides.

Prognostic Value of Gamma-Glutamyltransferase in Male Patients With Idiopathic Pulmonary Arterial Hypertension.

Background: The elevated gamma-glutamyltransferase (GGT) activity is regarded as an indicator of cardiovascular disease, with males having higher values than females. The greater incidence of idiopathic pulmonary arterial hypertension (IPAH) is observed in women, whereas prognosis is poor in men. The present study aims to investigate the potential association of GGT on male patients. Methods: Serum GGT levels were measured in 338 consecutive adult IPAH patients, who underwent bone morphogenetic protein receptor type 2 (BMPR2) genetic counseling, and matched with healthy subjects by sex and age. The followed interval was 48 ± 34 months. Results: Increased serum GGT levels were more common in patients with IPAH than controls (p < 0.001). GGT values were significantly higher in male patients than those of females (p < 0.001). Compared with female patients with BMPR2 mutation, GGT level in male patients with BMPR2 mutation was further increased (p = 0.002). Higher GGT levels were associated with worse hemodynamics and Nterminal pro B-type natriuretic peptide in all patients. However, males with a GGT concentration ≥ 53 U/L had a worse survival than those of females. Contrarily, if GGT concentration <53 U/L, there was no survival difference between male and female patients. After adjustment for relevant variables of clinical features and hemodynamics, baseline higher GGT levels remained increased risks of all-cause mortality in males rather than females. During rehospitalization follow-up, male patients still had significantly higher values of GGT than females. Conclusions: Increased GGT levels were correlated with BMPR2 mutation, hemodynamic dysfunction, and poor outcomes in male patients with IPAH. Further studies are needed to explain the origin of abnormal GGT and its potential pathogenesis in men.