[1]佟 瑞a,张 薇a,王 剑b,等.桥本甲状腺炎患者肠道菌群分布特征及其与甲状腺功能的关系研究[J].现代检验医学杂志,2024,39(03):60-66.[doi:10.3969/j.issn.1671-7414.2024.03.010]
　TONG Ruia,ZHANG Weia,WANG Jianb,et al.Study on Distribution Characteristics of Intestinal Flora and its Relationship with Thyroid Function in Patients with Hashimoto’s Thyroiditis[J].Journal of Modern Laboratory Medicine,2024,39(03):60-66.[doi:10.3969/j.issn.1671-7414.2024.03.010]
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桥本甲状腺炎患者肠道菌群分布特征及其与甲状腺功能的关系研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年03期
页码:
60-66
栏目:
论著
出版日期:
2024-05-15

文章信息/Info

Title:
Study on Distribution Characteristics of Intestinal Flora and its Relationship with Thyroid Function in Patients with Hashimoto’s Thyroiditis
文章编号:
1671-7414（2024）03-060-07
作者:
佟 瑞a; 张 薇a; 王 剑b; 吴 静c; 武文平a
（秦皇岛市中医医院 a. 检验科；b. 病理科；c. 体检科，河北秦皇岛 066000）
Author(s):
TONG Ruia; ZHANG Weia; WANG Jianb; WU Jingc; WU Wenpinga
(a. Department of Laboratory Medicine；b. Department of Pathology；c. Department of Physical Examination, Qinhuangdao Traditional Chinese Medicine Hospital, Hebei Qinhuangdao 066000，China)
关键词:
桥本甲状腺炎; 甲状腺功能; 肠道菌群分布特征
分类号:
R581.4；R446.5
DOI:
10.3969/j.issn.1671-7414.2024.03.010
文献标志码:
A
摘要:
目的 通过分析桥本甲状腺炎（Hashimoto’s thyroiditis，HT）患者肠道菌群分布特征及肠道菌群变化与HT 的相关性和对HT 发生的预测价值，为临床HT 诊疗提供参考。方法 选取秦皇岛市中医医院2022 年6 月～ 2023 年6 月收治的120 例HT 患者纳入观察组，另选择该院同期30 例健康体检者纳入对照组。两组均进行肠道菌群检测及甲状腺功能检测，对比两组及不同甲状腺功能HT 患者的肠道菌群α 多样性和门水平肠道菌群相对丰度，用Spearman 相关性分析HT 患者肠道菌群α 多样性及门水平肠道菌群相对丰度与血清甲状腺球蛋白抗体（anti-thyroglobulin antibodies，TgAb）、甲状腺过氧化物酶抗体（thyroid peroxidase antibodies, TPOAb）水平及甲状腺功能的相关性；用受试者工作特征（Receiver operating characteristic，ROC）曲线分析肠道菌群α 多样性及门水平肠道菌群相对丰度对HT 的预测效能。结果 与对照组比较，观察组的肠道菌群α 香农多样性指数（Shannon-wiener diversity index ，shannon）（4.66±0.61vs 5.21±0.46）和辛普森多样性指数（Simpson diversity index，simpson）（0.89±0.06 vs 0.93±0.07）均较低，差异有统计学意义（t=4.617，3.156，均P ＜ 0.05）；观察组的拟杆菌门的相对丰度（52.31 %±2.02 % vs 58.59 %±2.11 %）较低，厚壁菌门（37.15 %±2.43 % vs 33.46 %±2.56 %）、变形菌门（3.36 %±0.26 % vs 2.79 %±0.19 %）、梭杆菌门（1.02%±0.09 % vs 0.65 %±0.11 %）、放线菌门（1.01 %±0.12 % vs 0.57 %±0.13 %）和疣微菌门（0.82 %±0.11 % vs 0.41%±0.09 %）的相对丰度均较高，差异具有统计学意义（t=15.096，7.360，11.267，19.231，17.665，18.882，均P ＜ 0.001）；观察组的血清TgAb 水平（169.12±10.23 IU/ml vs 18.59±1.78 IU/ml）和TPOAb 水平（56.43±12.11 IU/ml vs 2.51±0.57IU/ml）均较高，差异具有统计学意义（t=80.097，24.319，均P ＜ 0.001）。该研究120 例HT 患者甲状腺功能正常者89 例、异常者31 例，与正常者比较，甲状腺功能异常者的肠道菌群α 多样性指数shannon（4.49±0.64 vs 4.83±0.58），simpson（0.87±0.07 vs 0.91±0.05）较低，差异有统计学意义（t=2.736，3.439，均P<0.05）；拟杆菌门相对丰度（49.10%±1.99 % vs 55.52 %±2.05 %）较低，厚壁菌门（38.87 %±2.60 % vs 35.43 %±2.26 %）、变形菌门（3.60 %±0.26 %vs 3.12 %±0.19 %）、梭杆菌门（1.15 %±0.09 % vs 0.89 %±0.11 %）和放线菌门（1.16 %±0.13 % vs 0.86 %±0.11 %）、疣微菌门（0.97 %±0.13 % vs 0.67 %±0.09 %）的相对丰度均较高，差异具有统计学意义（t=15.128，7.016，9.849，14.576，12.464，14.148，均P ＜ 0.001）。Spearman 相关性分析显示，HT 患者的肠道菌群α 多样性指数shannon，simpson 及拟杆菌门的相对丰度与血清TgAb，TPOAb 水平呈负相关（r=-0.436，-0.427，-0.402；-0.419，-0.456，-0.416，均P ＜ 0.001），与甲状腺功能均呈正相关（r=0.401，0.409，0.487，均P ＜ 0.001）；厚壁菌门、变形菌门、梭杆菌门、放线菌门和疣微菌门的相对丰度与血清TgAb，TPOAb 水平呈正相关（r=0.411，0.441，0.447，0.421，0.447；0.425，0.415，0.438，0.402，0.469，均P ＜ 0.001），与甲状腺功能呈负相关（r=-0.412，-0.417，-0.475，-0.463，-0.471，均P ＜ 0.001）。ROC 曲线分析显示，肠道菌群α 多样性指数shannon 预测HT 的最佳截断值、曲线下面积（areaunder curve，AUC）、敏感度、特异度、95 % 置信区间（95 % confidence interval，95 %CI）和约登指数分别为4.677，0.749，49.17 %，96.67 %，95 %CI（0.672~0.816），0.458；simpson 预测HT 的最佳截断值、曲线下面积、敏感度、特异度、95 % 置信区间和约登指数分别为0.940，0.644，80.00 %，53.33 %，95 % CI（0.562~0.721），0.333；simpson 和shannon 联合检测预测HT 的曲线下面积、敏感度、特异度、95 % 置信区间和约登指数分别为0.752，85.83 %，50.00 %，95%CI（0.664~0.810），0.462；门水平各肠道菌相对丰度联合检测预测HT 的AUC，敏感度、特异度、95 % 置信区间和约登指数分别为0.743，96.67 %，46.67 %，95 %CI（0.665~0.811），0.548。结论 HT 存在肠道菌群失调；肠道菌群失调与HT 患者的甲状腺细胞破坏、甲状腺功能异常有关；肠道菌群检测对HT 有预测效能。
Abstract:
Objective To explore the intestinal flora distribution characteristics in patients with Hashimoto’s thyroiditis (HT) and analyze the correlation between intestinal flora changes and HT and the predictive value on the occurrence of HT, so as to provide reference for clinical diagnosis and treatment of HT. Methods A total of 120 patients with HT admitted to Qinhuangdao Traditional Chinese Medicine Hospital from June 2022 to June 2023 were included in observation group, and 30 healthy physical examination subjects during the same period were enrolled as control group. Both groups performed intestinal flora detection and thyroid function detection. The α diversity and the relative abundance of intestinal flora at phylum level were compared between the two groups and among HT patients with different thyroid functions, and the correlation between α diversity of intestinal flora and relative abundance of intestinal flora at phylum level, serum levels of anti-thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) and thyroid function was analyzed by spearman correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficiency of α diversity and relative abundance of intestinal flora at phylum level on HT. Results Compared with control group, the intestinal flora α diversity indexes of shannon-wiener diversity index (shannon) and simpson diversity index (simpson) were lower in observation group [4.66±0.61 vs 5.21±0.46, 0.89±0.06 vs 0.93±0.07],and the differences were statistically significant (t=4.617, 3.156, P<0.05). The relative abundance of Bacteroidetes in observation group was lower than that in control group (52.31%±2.02% vs 58.59%±2.11%), while the relative abundances of Firmicutes, Proteobacteria, Fusobacteria, Actinobacteria and Verrucomicrobia were higher than those in control group （37.15%±2.43% vs 33.46%±2.56%, 3.36%±0.26% vs 2.79%±0.19%, 1.02%±0.09% vs 0.65%±0.11%, 1.01%±0.12% vs 0.57%±0.13%, 0.82%±0.11% vs 0.41%±0.09%), and the differences were statistically significant (t=15.096, 7.360, 11.267, 19.231, 17.665, 18.882, all P<0.001). The levels of serum TgAb (169.12±10.23 IU/ml vs 18.59±1.78 IU/ml) and TPOAb(56.43±12.11 IU/ml vs 2.51±0.57 IU/ml) in observation group were higher compared with those in control group, and the differences were statistically significant (t=80.097, 24.319, all P<0.001). Among 120 HT patients in this study, there were 89 cases with normal thyroid function and 31 cases with abnormal thyroid function. The intestinal flora α diversity indexes of shannon (4.49±0.64 vs 4.83±0.58), and simpson (0.87±0.07 vs 0.91±0.05) in patients with abnormal thyroid function were lower than those in normal patients, and the differences were statistically significant (t=2.736, 3.439, all P<0.05). The relative abundance of Bacteroides was lower (49.10%±1.99% vs 55.52%±2.05%), while the relative abundances of Firmicutes, Proteobacteria, Fusobacteria, Actinobacteria and Verrucomicrobia were higher than those in normal people (38.87%±2.60% vs 35.43%±2.26%, 3.60%±0.26% vs 3.12%±0.19%, 1.15%±0.09% vs 0.89%±0.11%, 1.16%±0.13% vs 0.86%±0.11%, 0.97%±0.13% vs 0.67%±0.09%)], and the differences were statistically significant (t=15.128, 7.016, 9.849, 14.576, 12.464, 14.148, all P<0.001). Spearman correlation analysis showed that the intestinal flora α diversity indexes （shannon and simpson） and relative abundance of Bacteroides in patients with HT were negatively correlated with serum TgAb and TPOAb levels (r= -0.436, -0.427, -0.402；-0.419, -0.456, -0.416, all P<0.001), but were positively correlated with thyroid function (r=0.401, 0.409, 0.487, all P<0.001). The relative abundances of Firmicutes, Proteobacteria, Fusobacteria, Actinobacteria and Verrucomicrobia were positively correlated with serum TgAb and TPOAb levels (r=0.411, 0.441, 0.447, 0.421, 0.447；0.425, 0.415, 0.438, 0.402, 0.469, all P<0.001), but were negatively correlated with thyroid function (r=-0.412, -0.417, -0.475, -0.463, -0.471, all P<0.001). ROC curve analysis revealed that the best cut-off value, the area under curve (AUC), sensitivity, specificity, 95% confidence interval (95%CI) and Youden index in shannon, simpson, combined detection of simpson and shannon, and the combined detection of relative abundance of intestinal bacteria at phylum level for predicting HT were 4.677, 0.749, 49.17%, 96.67%, 95%CI (0.672~0.816) and 0.458; 0.940, 0.644, 80.00%, 53.33%, 95%CI (0.562~0.721) and 0.333; 0.752, 85.83%, 50.00%, 95%CI (0.664~0.810) and 0.462; 0.743, 96.67%, 46.67%, 95%CI (0.665 ～ 0.811) and 0.548 ,respectively Conclusion HT had intestinal flora imbalance which was related to thyroid cell destruction and thyroid dysfunction in patients with HT. Intestinal flora detection has predictive efficiency on HT.

参考文献/References:

[1] 北京中西医结合学会甲状腺病专业委员会. 桥本甲状腺炎中西医结合诊疗北京专家共识(2021, 北京)[J]. 中国医药导报, 2022, 19(34): 4-7. Thyropathy Committee of Beijing Association of the Integrating of Traditional and Western Medicine. Beijing expert consensus on diagnosis and treatment of Hashimoto thyroiditis with integration of traditional and western medicine(2021,Beijing). [J]. China Medical Herald, 2022, 19(34): 4-7.
[2] 张国玉, 万会娜, 郭盼盼, 等. 桥本甲状腺炎发病因素及发病机制研究进展[J]. 新乡医学院学报, 2020,37(10): 984-989, 995. ZHANG Guoyu, WAN Huina, GUO Panpan, et al. Research progress on the etiology and pathogenesis of Hashimoto’s thyroiditis[J]. Journal of Xinxiang Medical University, 2020, 37(10): 984-989, 995.
[3] 王华, 史婷婷, 信中, 等. 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, et al. 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, 57(6): 931-939.
[4] 孙博文, 杨孟雪, 刘军, 等. Graves 病患者肠道菌群多样性分析[J]. 实用医学杂志,2020,36(6):767-773. SUN Bowen, YANG Mengxue, LIU Jun, et al. Diversity analysis of intestinal microbiota in Graves disease patients [J] Journal of Practical Medicine, 2020,36(6): 767-773.
[5] 赵勇, 邹倩, 夏方妹, 等. 基于16S rDNA 测序的自身免疫性甲状腺疾病患者肠道菌群研究[J]. 中国微生态学杂志, 2023, 35(7):765-771, 777. ZHAO Yong, ZOU Qian, XIA Fangmei, et al. Intestinal flora in patients with autoimmune thyroid disease based on 16S rDNA sequencing [J] . Chinese Journal of Microecology, 2023, 35(7):765-771, 777.
[6] 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. LIN Kai, QI Yuying, WANG Kaiyin, et al. Distribution of intestinal bacteria and its influence on Th17/Treg cells in patients with autoimmune thyroid disease[J].Chinese Journal of Microecology, 2022, 34(3): 318-322, 326.
[7] 葛均波, 徐永健, 王辰. 内科学[M]. 9 版. 北京：人民卫生出版社, 2018：693-694. GE Junbo, XU Yongjian, WANG Chen. Internal Medicine[M]. 9th Ed. Beijing: People’s Medical Publishing House, 2018:693-694.
[8] 陈孝平, 汪建平, 外科学[M] . 9 版. 北京: 人民卫生出版社,2018: 232. CHEN Xiaoping, WANG Jianping, Surgery [M]. 9th Ed. Beijing: People’s Medical Publishing House,2018:232.
[9] RAGUSA F, FALLAHI P, ELIA G, et al. Hashimotos’t hyroiditis: Epidemiology, pathogenesis, clinic and therapy[J]. Best Practice & Research Clinical Endocrinology & Metabolism, 2019, 33(6): 101367.
[10] 王安洋, 李超友, 薛刚, 等. 肠道菌群与甲状腺疾病的关系[J]. 山东大学耳鼻喉眼学报, 2023, 37(1):132-139. WANG Anyang, LI Chaoyou, XUE Gang, et al. Relationship between intestinal flora and thyroid diseases[J] . Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(1):132-139.
[11] 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.
[12] 高琳, 王婧颖, 马素芳, 等. 肠道菌群与甲状腺相关疾病关系的研究进展[J]. 山西医科大学学报, 2023,54(5): 707-710. GAO Lin, WANG Jingying, MA Sufang, et al. Research progress on the relationship between gut microbiota and thyroid-related diseases [J]. Journal of Shanxi Medical University, 2023, 54(5): 707-710.
[13] 赵慧, 梁梅花. 肠道菌群对自身免疫性甲状腺疾病发病影响的研究进展[J]. 山东医药, 2021, 61(8):105-108. ZHAO Hui, LIANG Meihua. Research progress on the impact of gut microbiota on the development of autoimmune thyroid diseases [J]. Shandong Medical Journal, 2021, 61(8): 105-108.
[14] 陈勋, 郝梦圆, 李荣海, 等. TPOAb, TgAb 检测在桥本氏甲状腺炎中的意义[J]. 国际检验医学杂志,2021, 42(21)：2619-2622, 2626. CHEN Xun, HAO Mengyuan, LI Ronghai, et al. Significance of TPOAb and TgAb detection in Hashimoto’s thyroiditis [J]. International Journal of Laboratory Medicine. 2018, 42(21): 2619-2622.
[15] 李曼曼, 兰丽珍. 肠道菌群与自身免疫性甲状腺疾病关系的研究进展[J]. 中国临床研究, 2020, 33(9):1278-1280, 1284. LI Manman, LAN Lizhen. Research progress on the relationship between gut microbiota and autoimmune thyroid diseases [J]. Chinese Journal of Clinical Research, 2020, 33(9): 1278-1280, 1284.
[16] 李思思. 不同舌苔类型桥本甲状腺炎患者的肠道菌群特点[D]. 武汉：湖北中医药大学, 2011：48-50. LI Sisi. Characteristics of intestinal microbiota in patients with Hashimoto’s thyroiditis with different types of tongue coating[D]. Wuhan：Hubei University of Chinese Medicine, 2011：48-50.
[17] 付佳闻, 李晓华, 张宏利, 等. 维生素D 缺乏与桥本甲状腺炎及相关因素的研究[J]. 内科理论与实践,2021, 16(1): 27-31. FU Jiawen, LI Xiaohua, ZHANG Hongli, et al. Study on the relationship between vitamin D deficiency and Hashimoto’s thyroiditis[J]. Journal of Internal Medicine Concepts & Practice, 2021, 16(1): 27-31.
[18] 李佩花, 王丽, 赵乃倩. 微量元素诱导桥本甲状腺炎发生发展的研究进展[J]. 新医学, 2023, 54(5): 307-311. LI Peihua, WANG Li, ZHAO Naiqian. Research progress on the incidence and progression of Hashimoto’s thyroiditis induced by trace elements[J].New Medicine, 2023, 54(5): 307-311.
[19] 李海燕, 刘强, 蒋丽, 等. 桥本甲状腺炎患者血清Tpo Ab, Tg Ab 水平在诊断和分型中的应用价值[J].中国实验诊断学, 2022, 26(2): 176-179. LI Haiyan, LIU Qiang, JIANG Li, et al. Application value of levels of serum Tpo Ab and Tg Ab in the diagnosis and classification of patients with Hashimoto’s thyroiditis[J]. Chinese Journal of Laboratory Diagnosis, 2022, 26(2): 176-179.
[20] 赵永峰, 杜杰, 胡峰, 等. 3 种甲状腺影像报告和数据系统对桥本甲状腺炎背景下甲状腺结节的诊断价值[J]. 中国超声医学杂志, 2023, 399(4): 365-368. ZHAO Yongfeng, DU Jie, HU Feng, et al. Diagnostic value of the three thyroid imaging reporting and data system for thyroid nodules in context of hashimoto thyroiditis[J]. Chinese Journal of Ultrasound in Medicine, 2023, 39(4): 365-368.

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　YU Diaoa,HU Lanb,XU Shi-penga,et al.Using Sigma-metric SQC Run Size Nomogram to Design a Multistage Quality Control Strategy for Thyroid Function Testing Items in Clinical Laboratory[J].Journal of Modern Laboratory Medicine,2023,38(03):190.[doi:10.3969/j.issn.1671-7414.2023.02.036 ]
[5]徐晓丽,闫莹玉,刁艳君,等.西安地区11~16岁健康青少年血清甲状腺功能指标参考范围建立及验证[J].现代检验医学杂志,2024,39(01):170.[doi:10.3969/j.issn.1671-7414.2024.01.032]
　XU Xiaoli,YAN Yingyu,DIAO Yanjun,et al.Establishment and Validation of Reference Range of Thyroid Function among Healthy 11 ～ 16 Year-old Teenagers in Xi’an[J].Journal of Modern Laboratory Medicine,2024,39(03):170.[doi:10.3969/j.issn.1671-7414.2024.01.032]

备注/Memo

备注/Memo:
基金项目：秦皇岛市科学技术研究与发展计划（202301A130）。
作者简介：佟瑞（1986-），女，硕士研究生，副主任检验技师，研究方向：甲状腺疾病中西医结合治疗，E-mail：tongrui4321@126.com。
通讯作者：武文平（1984-），男，硕士研究生，副主任检验技师，研究方向：甲状腺疾病实验室诊断，E-mail：erru312422194@163.com。
更新日期/Last Update: 2024-05-15