■本研究旨在探讨妊娠前半期甲状腺功能减退症患者肠道菌群特征与外周血辅助性T细胞(Th)1/Th2平衡的关系。
■采用流式细胞术测定甲状腺功能减退组和对照组孕妇外周血Th1/Th2比值。细胞计数珠阵列测定用于确定白细胞介素-2(IL-2)的血清水平,IL-4,IL-6,IL-10,肿瘤坏死因子(TNF)-α,和干扰素(IFN)-γ。此外,16SrRNA扩增子测序用于测定两组的肠道微生物组成。最后,肠道菌群之间的关系,Th1/Th2细胞,细胞因子,并对临床指标进行分析。
■甲状腺功能减退组的C反应蛋白水平高于对照组。与对照组相比,甲状腺功能减退组显示Th1细胞和Th1/Th2比值增加,Th2细胞减少。甲减组有较高的血清IL-2、TNF-α、和IFN-γ水平,降低IL-10水平,比对照组。甲状腺功能减退组肠道菌群的丰富度增加,而多样性降低。线性判别分析效应大小显示甲状腺功能减退症组有较高丰度的普氏菌和粪杆菌,但是拟杆菌的丰度较低,与对照组相比。Prevotella与Th1细胞呈正相关,Th1/2比率,和TNF-α。拟杆菌与Th2细胞和IL-10呈正相关,与Th1细胞呈负相关,Th1/2比率,TNF-α,和IFN-γ。甲状腺过氧化物酶抗体水平与TNF-α成正比。
■妊娠前半期甲状腺功能减退症患者会出现Th1/Th2失衡。肠道菌群紊乱可能通过影响Th1/Th2平衡而导致妊娠期甲状腺功能减退。
This study aimed to investigate the relationship between intestinal microflora characteristics and the peripheral blood T helper cell (Th)1/Th2 balance in patients with hypothyroidism during the first half of pregnancy.
The Th1/Th2 ratios in the peripheral blood of pregnant women in the hypothyroidism and control groups were determined using flow cytometry. The cytometric bead array assay was used to determine the serum levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Moreover, 16S rRNA amplicon sequencing was used to determine the intestinal microbial composition in the two groups. Finally, the relationships between intestinal microflora, Th1/Th2 cells, cytokines, and clinical indicators were analyzed.
C-reactive protein levels were higher in the hypothyroidism group than in the control group. In contrast to the control group, the hypothyroidism group showed an increase in Th1 cells and the Th1/Th2 ratio, and a decrease in Th2 cells. The hypothyroidism group had higher serum IL-2, TNF-α, and IFN-γ levels, and lower IL-10 levels, than the control group. The richness of the intestinal microflora in the hypothyroidism group increased whereas the diversity decreased. The linear discriminant analysis effect size revealed that the hypothyroidism group had a higher abundance of Prevotella and Faecalibacterium, but a lower abundance of Bacteroides, compared to the control group. Prevotella was positively correlated with Th1 cells, the Th1/2 ratio, and TNF-α. Bacteroides was positively correlated with Th2 cells and IL-10, but negatively correlated with Th1 cells, the Th1/2 ratio, TNF-α, and IFN-γ. The thyroid peroxidase antibody level was directly proportional to TNF-α.
A Th1/Th2 imbalance occurs in patients with hypothyroidism during the first half of pregnancy. Disorders of the intestinal microflora may lead to hypothyroidism during pregnancy by affecting the Th1/Th2 balance.