Graves病及Graves眼病患者治疗前后肠道菌群的变化研究  

Study on the Changes of Intestinal Flora in Patients with Graves′Disease and Graves′Ophthalmopathy Before and After Treatment

作　　者：韩香 徐茜 赵静 余雪婷 梁景童 石宏彩 鞠海兵 HAN Xiang;XU Qian;ZHAO Jing;YU Xueting;LIANG Jingtong;SHI Hongcai;JU Haibing(The Graduate School,Kunming Medical University,Kunming Yunan 650032,China)

机构地区：[1]昆明医科大学研究生院,云南昆明650032 [2]联勤保障部队920医院内分泌科

出　　处：《联勤军事医学》2024年第11期928-935,979,共9页Military Medicine of Joint Logistics

基　　金：云南省兴滇人才医疗卫生人才项目(XDYC-YLWS-2023-0098)。

摘　　要：目的探讨Graves病、Graves眼病患者治疗前后肠道菌群结构的变化及其与临床参数之间的关联性。方法选取2022-05/2023-08月在作者医院新诊断的Graves病、Graves眼病患者分别纳入Graves病组(n=20)和Graves眼病组(n=20),同期入选年龄及性别相匹配的健康人群作为对照组(n=20)。采集对照组与Graves病、Graves眼病组受试者治疗前后的血清和粪便样本,通过16SrRNA基因测序获得肠道菌群的信息,比较对照组与Graves病组和Graves眼病组治疗前后肠道菌群以及临床指标的变化。结果Graves病、Graves眼病、对照组3组受试者甲状腺功能指标、肝功能指标差异均有统计学意义(P均<0.05)。Graves病组及Graves眼病组患者肠道菌群的Alpha多样性较对照组明显下降,治疗后其多样性有一定改善。在门水平上,拟杆菌门在Graves病组、Graves眼病组中富集,变形菌门在对照组中富集,治疗后Graves病组、Graves眼病组较治疗前拟杆菌门降低(P均<0.05)。在属水平上,拟杆菌属、普雷沃菌属在Graves病组中富集,克雷伯菌属、Lachnoclostridium菌属在Graves眼病组中富集,粪杆菌属、真杆菌属、乳杆菌属在对照组中富集;治疗后Graves病组、Graves眼病组较治疗前真杆菌属、乳杆菌属水平增高、Lachnoclostridium菌属水平降低(P均<0.05)。Graves病组、Graves眼病组患者拟杆菌属与促甲状腺激素受体抗体(thyrotrophin receptor antibody,TRAb)、甲状腺素(thyroxine,T_(4))、三碘甲状腺原氨酸(triiodothyronine,T_(3)),Lachnoclostridium菌属与T_(4)、游离甲状腺素(free thyroxine,FT_(4))、游离三碘甲状腺原氨酸(free triiodothyronine,FT_(3))、T_(3)均呈正相关关系,真杆菌属与T_(4)、T_(3)均呈负相关关系。结论Graves病及Graves眼病患者肠道菌群的物种丰富度与物种多样性降低;肠道菌群的菌门及菌属比例失调;经治疗后肠道菌群有一定改善,但肠道菌群紊乱没有得到完全纠正。Objective To investigate the changes of intestinal flora structure in patients with Graves′disease and Graves′ophthalmopathy before and after treatment and the correlation with clinical parameters.Methods The newly diagnosed Graves′disease and Graves′ophthalmopathy patients in the author′s hospital from May 2022 to August 2023 were selected as the Graves′disease group(n=20)and Graves′ophthalmopathy group(n=20),and the healthy population matched to age and gender was selected as the control group(n=20).Serum and fecal samples were collected from the control group,Graves′disease and Graves′ophthalmopathy patients before and after treatment,and the information of intestinal microbiota was obtained by 16SrRNA gene sequencing,and the changes of intestinal microbiota and clinical indicators before and after treatment were compared among the control group,Graves′disease group and Graves′ophthalmopathy group.Results There were statistically significant differences in thyroid function indexes and liver function indexes among the three groups(all P<0.05).Compared with the healthy control group,the Alpha diversity of intestinal microbiota in the Graves disease group and the Graves′ophthalmopathy group was significantly lower(all P<0.05),and its diversity improved to a certain extent after treatment.At the phylum level,Bacteroidota were enriched in the Graves disease group and Graves′ophthalmopathy group,and Proteobacteria were enriched in the control group.The Bacteroidota in the Graves′disease group and Graves′ophthalmopathy group were lower than those before treatment(all P<0.05).At the genus level,Bacteroides and Prevotella were enriched in Graves′disease group,Klebsiella and Lachnoclostridium were enriched in Graves′ophthalmopathy group,and Faecalibacterium,Eubacterium and Lactobacillus were enriched in the control group;after treatment,the levels of Eubacterium and Lactobacillus in the Graves′disease group and and Graves′ophthalmopathy group were higher than those before treatment,

关 键 词：GRAVES病 GRAVES眼病 肠道菌群 16SrRNA基因测序 Alpha多样性 菌门 菌属 

分 类 号：R581.1[医药卫生—内分泌]