妊娠期糖尿病孕妇糖脂代谢状态对新生儿免疫功能、胎便菌群、炎症因子的影响

Effects of glucose and lipid metabolic status in pregnant women with gestational diabetes mellitus on neonatal immune function, meconium microbiota, and inflammatory factors

摘要

目的 分析妊娠期糖尿病(GDM)孕妇糖脂代谢状态对新生儿免疫功能、肠道菌群、炎症因子的影响。方法 选取2021年3月至2023年3月于某院收治的GDM孕妇87例为GDM组,同期选取某院产检及分娩的健康孕妇87例为对照组.采用t检验比较两组孕妇的糖脂代谢水平以及两组新生儿(24h内)炎症因子、肠道菌群以及免疫功能的差异,并采用Pearson相关性分析GDM孕妇糖脂代谢水平与新生儿各项指标的相关性。结果 GDM组餐后2h血糖(2hPBG)、空腹血糖(FBG)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)指标均高于对照组(t值范围为2.846~6.178,均P<0.05),高密度脂蛋白胆固醇(HDL-C)低于对照组(t值为3.788,P<0.05).GDM组新生儿白细胞介素6(IL-6)、白细胞介素10(IL-10)均高于对照组(t值分别为42.206、25.671,均P<0.05).GDM组新生儿变形菌门相对丰度高于对照组(χ²值为3.937,P<0.05);厚壁菌门相对丰度、Shannon指数、Simpson指数均低于对照组(χ²/t值分别为4.143、3.610、5.786,均P<0.05).GDM组新生儿CD8⁺T淋巴细胞高于对照组(t值为6.678,P<0.05),CD4⁺T淋巴细胞、CD4⁺/CD8⁺、免疫球蛋白A(IgA)、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)低于对照组(t值范围为6.045~11.462,均P<0.05).Pearson相关性分析显示,GDM组孕妇HDL-C与新生儿IL-6、IL-10、CD4⁺、CD4⁺/CD8⁺、厚壁菌门相对丰度、Shannon指数、Simpson指数、IgA、IgG、IgM均呈正相关(r值范围在0.327~0.713之间,均P<0.05),与变形菌门相对丰度、CD8⁺均呈负相关(r值分别为-0.412、-0.722,均P<0.05);而GDM组孕妇2hPBG、FBG、TG、TC、LDL-C与新生儿IL-6、IL-10、厚壁菌门相对丰度、Shannon指数、Simpson指数以及CD4⁺、CD4⁺/CD8⁺、IgA、IgG、IgM均呈负相关(r值范围分别在-0.552~-0.238、-0.664~-0.214、-0.727~-0.229、-0.649~-0.201、-0.724~-0.279之间,均P<0.05),与变形菌门相对丰度、CD8⁺均呈正相关(r值范围分别为0.596~0.658、0.423~0.424、0.587~0.641、0.419~0.442、0.428~0.574,均P<0.05)。结论 妊娠期糖尿病孕妇糖脂代谢存在紊乱现象,可影响新生儿的肠道菌群、免疫功能,且新生儿易合并感染.

Abstract

Objective To analyze the effects of glucose and lipid metabolism status in pregnant women with gestational diabetes mellitus (GDM) on neonatal immune function, intestinal flora, and inflammatory factors. Methods A total of 87 pregnant women with GDM admitted to Xingtai Central Hospital from March 2021 to March 2023 were selected as GDM group, and 87 healthy pregnant women with normal prenatal examination and delivery were selected as control group. The t-test was used to compare the differences in glucose and lipid metabolism levels between the two groups of pregnant women, as well as the differences in inflammatory factors, intestinal flora, and immune function of neonates (within 24 hours after birth) between the two groups. Pearson correlation analysis was used to analyze the correlation between glucose and lipid metabolism levels of GDM pregnant women and various neonatal indicators. Results The indexes of postprandial 2-hour blood glucose (2hPBG), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in GDM group were higher than those in control group (t=2.846-6.178, P<0.05), while high-density lipoprotein cholesterol (HDL-C) was lower than that in control group (t=3.788, P<0.05). Neonates in the GDM group had significantly higher levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) compared with controls (t=42.206 and 25.671, respectively, P<0.05). The relative abundance of Proteobacteria was higher in the GDM group (χ²=3.937, P<0.05), whereas the relative abundance of Firmicutes, Shannon index, and Simpson index were lower (χ²/t=4.143, 3.610 and 5.786, respectively, P<0.05). The proportion of CD8⁺ T lymphocytes in neonates was higher in the GDM group (t=6.678, P<0.05), while CD4⁺ T lymphocytes, CD4⁺/CD8⁺ ratio, and immunoglobulins A, G, and M (IgA, IgG, IgM) were all lower than in the control group (t=6.045-11.462, P<0.05). Pearson correlation analysis showed that maternal HDL-C in GDM group was positively correlated with neonatal IL-6, IL-10, relative abundance of Firmicutes, Shannon index, Simpson index, CD4⁺, CD4⁺/CD8⁺, IgA, IgG and IgM (r=0.327-0.713, P<0.05), but negatively correlated with relative abundance of Proteobacteria and CD8⁺ (r=-0.412, -0.722, respectively, P<0.05). In GDM group, 2hPBG, FBG, TG, TC and LDL-C were negatively correlated with neonatal IL-6, IL-10, relative abundance of Firmicutes, Shannon index, Simpson index, CD4⁺, CD4⁺/CD8⁺, IgA, IgG and IgM (the ranges of r were -0.552 to -0.238, -0.664 to -0.214, -0.727 to -0.229, -0.649 to -0.201, and -0.724 to -0.279, respectively, P<0.05), but positively correlated with relative abundance of Proteobacteria and CD8⁺ (the ranges of r were 0.596 to 0.658, 0.423 to 0.424, 0.587 to 0.641, 0.419 to 0.442, and 0.428 to 0.574, respectively, P<0.05). Conclusion Pregnant women with GDM exhibit disturbances in glucose and lipid metabolism, which can adversely affect neonatal intestinal microbiota composition and immune function, increasing susceptibility to infection in newborns.

关键词

妊娠期糖尿病 / 糖脂代谢 / 新生儿 / 炎症因子 / 肠道菌群 / 免疫功能

Key words

gestational diabetes mellitus / glucose and lipid metabolism / neonate / inflammatory factor / intestinal microbiota / immune function

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基金资助

邢台市重点研发计划自筹项目(2022ZC175)