目的·探索妊娠期糖尿病（gestational diabetes mellitus，GDM）女性在孕中期至孕晚期的肠道菌群变化特征，及其与膳食摄入、血糖及血脂水平的相关性。方法·2019年6月—2021年1月于上海中医药大学附属第七人民医院妇产科门诊招募定期产检的孕中期女性78人，其中GDM女性30人（GDM组）、健康妊娠女性48人（对照组）。收集并分析2组孕妇的人口学信息及血生化指标。采用半定量食物频率问卷对2组孕妇的膳食摄入情况进行比较。分别于孕中期、孕晚期收集2组孕妇的粪便样本，通过16S rRNA 高通量测序比较孕中期、孕晚期的GDM组和对照组孕妇的肠道菌群特征和其相似性。通过Spearman相关性热图分析孕中期孕妇的肠道菌群丰度与环境因子（血生化指标、膳食摄入成分）的关联。结果·与对照组相比，GDM组孕妇的孕期增重较多（P=0.012）。在孕中期，GDM组孕妇的空腹血糖水平、口服葡萄糖耐量试验（oral glucose tolerance test，OGTT） 1 h和OGTT 2 h血糖水平、三酰甘油水平高于对照组，高密度脂蛋白和低密度脂蛋白水平低于对照组（均P<0.05）。孕期膳食摄入的结果显示，GDM组孕妇的脂肪摄入水平高于对照组（P=0.046）。从孕中期至孕晚期，GDM组和对照组孕妇的肠道菌群α-多样性、β-多样性间差异均无统计学意义。孕中期GDM组与孕晚期GDM组、孕中期对照组、孕晚期对照组的属水平菌群结构相似性最小，而孕晚期GDM组与对照组的菌属构成相似性最高。Spearman相关性热图的结果显示，丁酸球菌科（Butyricicoccaceae）的丰度与膳食纤维和蔬菜摄入水平呈正相关（r=0.365，P=0.024；r=0.469，P=0.003），克雷伯菌（Klebsiella）的丰度与三酰甘油水平呈正相关（r=0.329，P=0.044），双歧杆菌（Bifidobacterium）的丰度与OGTT 2 h血糖水平呈负相关（r=-0.364，P=0.025）。结论·孕中期GDM组和对照组孕妇的肠道菌群组成较孕晚期存在较多显著差异物种，孕中期GDM相关的肠道菌群失调可能与糖脂代谢，膳食脂肪和蔬菜摄入水平存在关联。

Objective ·To explore the changes of gut microbiota in the women with gestational diabetes mellitus (GDM) during the second to the third trimesters of pregnancy, and the correlation with dietary intake and glucose-lipid metabolism. Methods ·From June 2019 to January 2021, 78 pregnant women (30 GDM women in the GDM group and 48 healthy women in the control group) in the second trimester of pregnancy were recruited from the Department of Obstetrics and Gynecology of Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine. Demographic information and blood biochemical indicators of the two groups were collected and analyzed. A semi-quantified Food-Frequency Questionnaire (FFQ) was used to compare the dietary intake of the two groups of pregnant women. Fecal samples were collected in both groups at the second and the third trimesters of pregnancy, respectively. The characteristics and similarities of gut microbiota in both groups at the second and the third trimesters were compared by 16S rRNA high-throughput sequencing. Spearman correlation heatmap was used to analyze the relation between the abundance of gut microbiota and environmental factors (blood biochemical indicators and dietary intake components) in the pregnant women at the second trimester. Results ·Compared with the control group, the women in the GDM group gained more weight during pregnancy (P=0.012). In the second trimester, compared with the control group, the fast blood glucose level, the blood glucose level at oral glucose tolerance test (OGTT) 1 h and 2 h, and the triacylglycerol level of the pregnant women in the GDM group were higher, and the high-density lipoprotein and the low-density lipoprotein levels were lower (all P<0.05). The results of dietary intake during pregnancy showed that the fat intake level of the pregnant women in the GDM group was higher than that in the control group (P=0.046). From the second to the third trimester of pregnancy, there was no significant difference in the α-diversity and β-diversity of gut microbiota between the GDM group and the control group. The gut bacterial composition at genus level of the GDM group at the second trimester had the least similarity with that of the other three groups (GDM group at the third trimester, control group at the second trimester and the third trimester), while the GDM group and control group had the most similar gut bacterial composition at genus level in the third trimester. Spearman correlation heatmap analysis showed that the abundance of Butyricicoccaceae was positively correlated with dietary fiber and vegetable intake level (r=0.365, P=0.024; r=0.469, P=0.003), the abundance of Klebsiella was positively correlated with triacylglycerol level (r=0.329, P=0.044), and the abundance of Bifidobacterium was negatively correlated with blood glucose level at OGTT 2 h (r=-0.364, P=0.025). Conclusion ·The composition of gut microbiota of pregnant women in the GDM group and control group in the second trimester of pregnancy is significantly different from that in the third trimester of pregnancy. The disorder of gut microbiota related to GDM in the second trimester of pregnancy may be related to glucose-lipid metabolism, dietary fat and vegetable intake level.