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妊娠晚期甲状腺功能减退合并甲状腺过氧化物酶抗体异常患者肠道菌群的生物学特征
侯晓峰,许雅娟*,张淼,王彪,孙宗宗,班彦杰
0
(郑州大学第三附属医院产科, 郑州 450052
*通信作者)
摘要:
目的 分析妊娠晚期甲状腺功能减退合并甲状腺过氧化物酶抗体(TPOAb)水平异常患者的肠道菌群生物学特征及其与母婴结局的相关性。方法 选择2018年9月至2019年10月在我院产科门诊就诊的TPOAb水平异常(>35 IU/mL,TPOAb阳性组)和TPOAb水平正常(≤35 IU/mL,TPOAb阴性组)的妊娠晚期甲状腺功能减退孕妇各20例作为研究对象。采用16S rRNA测序技术比较两组孕妇肠道菌群的种类及相对丰度,并通过qRT-PCR技术对双歧杆菌属和毛螺菌属进行定量分析。比较两组孕妇的血清学检验指标和母婴临床指标等,并分析孕妇肠道菌群和母婴结局的相关性。结果 16S rRNA测序结果显示TPOAb阳性组孕妇肠道菌群中双歧杆菌属的相对丰度增高,毛螺菌属的相对丰度降低,qRT-PCR分析结果也验证了这一变化。血清学指标检测结果显示,TPOAb阳性组产前CRP、IL-2和IL-6水平及产后CRP水平均高于TPOAb阴性组(P均<0.05)。相关性分析结果显示,双歧杆菌属相对丰度与血清TPOAb水平呈正相关(r=0.55,P<0.01),毛螺菌属相对丰度与血清IL-6水平呈负相关(r=-0.37,P=0.02)。TPOAb阳性组既往胚胎停育次数和自然流产次数均多于TPOAb阴性组(P=0.04、0.02)。TPOAb阳性组新生儿体重、新生儿头围均低于TPOAb阴性组(P均<0.01),分娩时新生儿窒息和新生儿窘迫的发生率均高于TPOAb阴性组(P均=0.04)。结论 妊娠晚期甲状腺功能减退孕妇TPOAb异常与肠道菌群及不良的母婴结局密切相关。肠道双歧杆菌属和毛螺菌属可能成为妊娠晚期甲状腺功能减退孕妇TPOAb异常的无创生物标志物。
关键词:  妊娠晚期  甲状腺功能减退症  甲状腺过氧化物酶抗体  16S核糖体RNA  肠道菌群
DOI:10.16781/j.0258-879x.2021.08.0858
投稿时间:2021-04-24修订日期:2021-06-24
基金项目:河南省科技厅科技攻关项目(182102410020).
Biological characteristics of intestinal flora in hypothyroidism patients with abnormal thyroperoxidase antibodies in the third trimester of pregnancy
HOU Xiao-feng,XU Ya-juan*,ZHANG Miao,WANG Biao,SUN Zong-zong,BAN Yan-jie
(Department of Obstetrics, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
*Corresponding author)
Abstract:
Objective To analyze the biological characteristics of intestinal flora in hypothyroidism patients with abnormal thyroperoxidase antibodies (TPOAb) in the third trimester of pregnancy and their correlations with maternal and infant outcomes. Methods A total of 40 hypothyroidism patients in the third trimester of pregnancy (20 with abnormal TPOAb level [>35 IU/mL] and 20 with normal TPOAb level [≤35 IU/mL]) who visited in the Department of Obstetrics of our hospital from Sep. 2018 to Oct. 2019 were selected. The species and relative abundance of intestinal flora between the 2 groups were compared by 16S rRNA sequencing, and Bifidobacterium and Lachnospira were quantitatively analyzed by quantitative real-time ploymerase chain reaction (qRT-PCR). In addition, the serological test indexes and maternal and infant clinical indexes of the 2 groups were compared, and the correlation between maternal intestinal flora and maternal and infant outcomes was analyzed. Results 16S rRNA sequencing showed that the relative abundance of Bifidobacterium in the intestinal flora of TPOAb positive pregnant women was increased, while the relative abundance of Lachnospira was decreased. qRT-PCR analysis also confirmed this change. The results of serological indexes showed that the levels of C reactive protein (CRP), interleukin (IL)-2 and IL-6 before delivery and the level of CRP after delivery were significantly higher in the TPOAb positive group than in the TPOAb negative group (all P<0.05). Correlation analysis showed that the relative abundance of Bifidobacterium was positively correlated with the serum TPOAb level (r=0.55, P<0.01), and the relative abundance of Lachnospira was negatively correlated with the serum IL-6 level (r=-0.37, P=0.02). The times of previous embryo suspension and spontaneous abortion of the TPOAb positive group were significantly higher than those of the TPOAb negative group (P=0.04 and 0.02). The neonatal weight and head circumference of the TPOAb positive group were significantly lower than those of the TPOAb negative group (both P<0.01), and the incidences of neonatal asphyxia and neonatal distress during delivery were significantly higher than those of the TPOAb negative group (both P=0.04). Conclusion The abnormal TPOAb of hypothyroid pregnant women in the third trimester of pregnancy is closely related to the intestinal flora and poor maternal and infant outcomes. Intestinal Bifidobacterium and Lachnospira may be noninvasive biomarkers for abnormal TPOAb in pregnant women with hypothyroidism in the third trimester of pregnancy.
Key words:  the third trimester of pregnancy  hypothyroidism  thyroperoxidase antibody  16S ribosomal RNA  intestinal flora