Graves病患者促甲状腺素受体抗体与肠道菌群及短链脂肪酸的相关性

doi:10.3969/j.issn.1006-7795.2022.06.018

首都医科大学学报 ›› 2022, Vol. 43 ›› Issue (6): 931-939.doi: 10.3969/j.issn.1006-7795.2022.06.018

Graves病患者促甲状腺素受体抗体与肠道菌群及短链脂肪酸的相关性

王华¹, 史婷婷², 信中², 华琳³, 李聪¹, 曹秋梅^1*

1.首都医科大学附属北京同仁医院南区急诊科,北京 102600;
2.首都医科大学附属北京同仁医院内分泌科,北京 102600;
3.首都医科大学生物工程学院生物医学信息学系,北京 100069

收稿日期:2022-06-27 出版日期:2022-12-21 发布日期:2022-11-30
基金资助:
北京市医管局“培育计划”项目(PX2021006), 首都医科大学校培育基金(PYZ21090),首都医科大学附属北京同仁医院青年人才院内种子基金(2020-YJJ-ZZL-012)。

Correlation study between thyrotropin receptor antibodies (TRAb) and intestinal flora and short-chain fatty acids in patients with Graves disease

Wang Hua¹, Shi Tingting², Xin Zhong², Hua Lin³, Li Cong¹, Cao Qiumei^1*

1. Department of Emergency, Beijing Tongren Hospital, Capital Medical University, Beijing 102600, China;
2. Department of Endocrinology, Beijing Tongren Hospital,Capital Medical University, Beijing 102600, China;
3. Department of Mathematics, School of Biomedical Engineering, Capital Medical University, Beijing 100069, China

Received:2022-06-27 Online:2022-12-21 Published:2022-11-30
Contact: ^*E-mail:honeydoc@126.com

摘要/Abstract

摘要： 目的探讨甲状腺功能正常的Graves病患者与健康对照者之间粪便肠道菌群结构及短链脂肪酸的差异,并明确促甲状腺素受体抗体(thyrotropin receptor auto-antibodies,TRAb)与差异菌群的相关性。方法选取30名治疗后甲状腺功能恢复正常的Graves病患者和32名健康对照者为研究对象,采用16S rRNA测序分析肠道菌群构成,气相色谱-质谱联用法(gas chromatography-mass spectrometry, GC-MS)方法测定短链脂肪酸浓度,分析TRAb抗体滴度与差异菌群的相关性。结果与对照组比较,Graves组患者的肠道菌群α多样性指数显著降低。在科水平,Graves组患者的拟杆菌(Bacteroidaceae)及瘤胃球菌(Ruminococcaceae) 等相对丰度下降,普雷沃菌(Prevotellaceae)及韦荣球菌(Erysipelotrichaceae)丰度升高。在种水平,Graves组患者的霍氏真杆菌(Eubacterium _hallii)、瘤胃球菌及反刍动物真杆菌(Eubacterium-ventriosum)相对丰度升高,而瘤胃球菌(Ruminococcus-bicirculans)及普通拟杆菌(Bacteroide_vulgatus)等丰度下降,差异均有统计学意义。LEfSe分析显示,Graves组普雷沃菌(f_Prevotellaceae及g_unidentified_Prevotellaceae)及厌氧菌(s_Prevotella copri)富集。作为肠道菌群的重要代谢产物,Graves组患者的丙酸及丁酸浓度显著下降,丙酸浓度与瘤胃球菌丰度正相关。关联分析显示,血清TRAb抗体滴度与瘤胃球菌丰度呈负相关。结论即使甲状腺功能恢复正常,Graves病患者的肠道菌群及丙酸等浓度仍发生显著性改变,这一改变可能与血清TRAb抗体滴度相关。

关键词: Graves病, 促甲状腺素受体抗体, 肠道菌群, 短链脂肪酸, 16S rRNA测序

Abstract: Objective To investigate the differences in intestinal microbiota and short-chain fatty acids between patients suffering from Graves disease (GD) with normal thyroid function and healthy controls, and to analyze the correlation between thyrotropin receptor auto-antibodies (TRAb) and different intestinal microbiota. Methods Totally 30 Graves patients with normal thyroid function (GD group) and 32 healthy controls (Control) were enrolled in our study.Feces were collected, and 16S rRNA sequencing was used to analyze the structure of intestinal bacteria, and gas chromatography-mass spectrometry (GC-MS) was used to determine the content of short-chain fatty acids, the relationship between TRAb and intestinal microbiota was analyzed. Results Compared with the control group, α-diversity indexes of intestinal flora in GD patients were significantly decreased statistically.At the family level, the abundance of Bacteroidaceae and Ruminococcaceae decreased in GD patients, while the abundance of Prevotellaceae and Erysipelotrichaceae increased.At the species level, Eubacterium _hallii, Ruminococcus and Eubacterium_ventriosum were increased in GD patients, whileRuminococcus-bicirculans and Bacteroide_vulgatus decreased, and the differences were statistically significant.LEfSe analysis showed that Prevotellaceae (f_prevotellaceae and g_unidentified_prevotellaceae) and anaerobic bacteria (s_Prevotella copri) were enriched in GD group.The levels of propionic acid and butyric acid in GD patients were significantly decreased.The level of propionic acid was positively correlated with the abundance of Ruminococcaceae. Our analysis showed that serum TRAb antibody was inversely correlated with Ruminococcus abundance. Conclusion Even if the thyroid function of patients with Graves disease was normal, the intestinal flora and levels of propionic acid in patients were still significantly changed, and this change may be related to the serum TRAb antibody.

Key words: Graves disease, thyrotropin receptor auto-antibodies (TRAb), intestinal bacteria, short-chain fatty acids, 16S rRNA

中图分类号:

R581

王华, 史婷婷, 信中, 华琳, 李聪, 曹秋梅. Graves病患者促甲状腺素受体抗体与肠道菌群及短链脂肪酸的相关性[J]. 首都医科大学学报, 2022, 43(6): 931-939.

Wang Hua, Shi Tingting, Xin Zhong, Hua Lin, Li Cong, Cao Qiumei. Correlation study between thyrotropin receptor antibodies (TRAb) and intestinal flora and short-chain fatty acids in patients with Graves disease[J]. Journal of Capital Medical University, 2022, 43(6): 931-939.

参考文献

[1] Rojas C, Gálvez-Jirón F, De Solminihac J, et al. Crosstalk between body microbiota and the regulation of immunity[J]. J Immunol Res, 2022, 2022: 6274265.
[2] Xu Z L, Jiang W, Huang W L, et al. Gut microbiota in patients with obesity and metabolic disorders-a systematic review[J]. Genes Nutr, 2022, 17(1): 2.
[3] Ma J Y, Piao X S, Mahfuz S, et al. The interaction among gut microbes, the intestinal barrier and short chain fatty acids[J]. Anim Nutr, 2021, 9: 159－174.
[4] Laudes M, Geisler C, Rohmann N, et al. Microbiota in health and disease-potential clinical applications[J]. Nutrients, 2021, 13(11): 3866.
[5] Martin-Gallausiaux C, Marinelli L, Blottière H M, et al. SCFA: mechanisms and functional importance in the gut[J]. Proc Nutr Soc, 2021, 80(1): 37－49.
[6] De Freitas Cayres L C, De Salis L V V, Rodrigues G S P, et al. Detection of alterations in the gut microbiota and intestinal permeability in patients with hashimoto thyroiditis[J]. Front Immunol, 2021, 12: 579140.
[7] Knezevic J, Starchl C, Tmava Berisha A, et al. Thyroid-gut-axis: how does the microbiota influence thyroid function?[J]. Nutrients, 2020, 12(6): 1769.
[8] Jiang W, Yu X Q, Kosik R O, et al. Gut microbiota may play a significant role in the pathogenesis of Graves' disease[J]. Thyroid, 2021, 31(5): 810－820.
[9] 孙博文, 杨孟雪, 杨波, 等. 肠道菌群在自身免疫性甲状腺疾病发生中的作用机制研究进展[J]. 山东医药, 2019, 59(33): 88－91.
[10] Shi T T, Xin Z, Hua L, et al. Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy[J]. J Endocrinol Invest, 2021, 44(2): 297－310.
[11] 林凯, 齐育英, 王开银, 等. 免疫性甲状腺疾病患者肠道菌群分布及其对Th17/Treg细胞的影响[J]. 中国微生态学杂志, 2022, 34(3): 318－322, 326.
[12] Virili C, Centanni M. “With a little help from my friends”-the role of microbiota in thyroid hormone metabolism and enterohepatic recycling[J]. Mol Cell Endocrinol, 2017, 458: 39－43.
[13] Zheng S J, Luo Y, Xiao J H. The impact of intestinal microorganisms and their metabolites on type 1 diabetes mellitus[J]. Diabetes Metab Syndr Obes, 2022, 15: 1123－1139.
[14] Valder S, Brinkmann C. Exercise for the diabetic gut-potential health effects and underlying mechanisms[J]. Nutrients, 2022, 14(4): 813.
[15] Campos-Perez W, Martinez-Lopez E. Effects of short chain fatty acids on metabolic and inflammatory processes in human health[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2021, 1866(5): 158900.
[16] Su X H, Yin X L, Liu Y, et al. Gut dysbiosis contributes to the imbalance of Treg and Th17 cells in Graves' disease patients by propionic acid[J]. J Clin Endocrinol Metab, 2020, 105(11): dgaa511.
[17] Stumpff F, Manneck D, Martens H. News in caecal signalling: the role of propionate in microbial-epithelial crosstalk[J]. Pflugers Arch, 2021, 473(6): 853－854.
[18] Yan S H, Chang J Y, Hao X H, et al. Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora[J]. Phytomedicine, 2022, 102: 154217.
[19] Peña-Rodríguez M, Vega-Magaña N, García-Benavides L, et al. Butyrate administration strengthens the intestinal epithelium and improves intestinal dysbiosis in a cholestasis fibrosis model[J]. J Appl Microbiol, 2022, 132(1): 571－583.
[20] Nguyen T D, Hållenius F F, Lin X, et al. Monobutyrin and monovalerin affect brain short-chain fatty acid profiles and tight-junction protein expression in ApoE-knockout rats fed high-fat diets[J]. Nutrients, 2020, 12(4): 1202.

Graves病患者促甲状腺素受体抗体与肠道菌群及短链脂肪酸的相关性

Correlation study between thyrotropin receptor antibodies (TRAb) and intestinal flora and short-chain fatty acids in patients with Graves disease

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 4

编辑推荐

Metrics

本文评价

[1]	安宇, 边南南, 丁小雨, 常晓娜, 刘佳, 王广. 1型糖尿病伴认知功能损伤小鼠脑组织肠道菌群代谢物的改变[J]. 首都医科大学学报, 2022, 43(4): 622-629.
[2]	马超, 贺毅, 孙作厘, 刘鑫垚, 冯正田, 陈沛, 宁艳哲, 朱虹, 尹冬青, 贾竑晓. 基于16S rRNA技术分析石珍安神汤对脱髓鞘小鼠肠道菌群多样性的影响[J]. 首都医科大学学报, 2020, 41(1): 64-70.
[3]	刘薇;袁申元;王雪;潘素芳;于湄;谢荣荣. Graves病患者胰岛素、真胰岛素变化与糖耐量的关系[J]. 首都医科大学学报, 2004, 25(1): 78-81.
[4]	任继平;王雪;田剑;林愈之;于湄. Graves病患者骨代谢变化的早期检测[J]. 首都医科大学学报, 1999, 20(3): 186-188.