Dynamic changes in the gut microbiota during three consecutive trimesters of pregnancy and their correlation with abnormal glucose and lipid metabolism

Abstract

Introduction: During normal pregnancy, changes in the gut microbiota (GM) in response to physiological alterations in hormonal secretion, immune functions and homeostasis have received extensive attention. However, the dynamic changes in the GM during three consecutive trimesters of pregnancy and their relationship with glucose and lipid metabolism have not been reported. In this study, we aimed to investigate the dynamic changes in the diversity and species of the GM during three consecutive trimesters in women who naturally conceived, and their relationships with abnormal fasting blood glucose (FBG) and serum lipid levels.

Methods: A total of 30 pregnant women without any known chronic or autoimmune inflammatory disease history before pregnancy were enrolled during the first trimester. Serum and stool samples were collected during the first trimester, the second trimester, and the third trimester. Serum samples were tested for FBG and blood lipid levels, and stool specimens were analyzed by 16S rDNA sequencing.

Results: The abundance ratio of bacteroidetes/firmicutes showed an increasing tendency in most of the subjects (19/30, 63.3%) from the first to the third trimester. LEfSe analysis showed that the abundance of Bilophila was significantly increased from the first to the third trimester. In addition, at the genus level, the increased relative abundance of Mitsuokella, Clostridium sensu stricto and Weissella were potentially involved in the development of high FBG during pregnancy. The raised relative abundance of Corynebacterium, Rothia and Granulicatella potentially contributed to the occurrence of dyslipidemia during pregnancy.

Conclusions: There are dynamic changes in the GM during the three trimesters, and the alterations in some bacterium abundance may contribute to the development of high FBG and dyslipidemia during pregnancy. Monitoring enterotypes and correcting dysbiosis in the first trimester may become new strategies for predicting and preventing glucolipid metabolism disorders during pregnancy.

Keywords: Glucose and lipid metabolism; Gut microbiota; Pregnancy.

Fig. 1

Composition of gut microbiota at phylum level in all subjects studied during the three trimesters of pregnancy. Histogram of gut microbiota (GM) composition in each subject at phylum level during the first trimester (T1), the second trimester (T2) and the third trimester (T3) (A); Dynamic change in the abundance ratio of Bacteroidetes/Firmicutes (B/F) in each subject from T1 to T3 (B). There was an overall increasing trend in B/F value from T1 (red), T2 (green) to T3 (blue) in 19 women, and no increasing trend from T1 (yellow), T2 (green) to T3 (blue) in the rest 11 women

Fig. 2

Differentially abundant taxa of gut microbiota in all the subjects across the three trimesters of pregnancy. There were significant differences in the abundance taxa of gut microbiota (GM) by linear discrimination analysis effect size (LEfSe) analysis [linear discrimination analysis (LDA) score > 2.0] between the first trimester (T1) and the second trimester (T2) (A), and between T1 and the third trimester (T3) (B)

Fig. 3

Differentially abundant taxa of gut microbiota with the dynamic change in FBG level across the three trimesters. There were significant differences by linear discrimination analysis effect size (LEfSe) analysis between WNG and ENG groups in the first trimester (T1, A) and the third trimester (T3, B), between WNG and LNG groups in T1 (C) and T3 (D), between WNG and WHG groups in T1 (E) and T3 (F), between WHG and ENG groups in T1 (G) and T3 (H), between WHG and LNG groups in T1 (I). FBG: fasting blood glucose, WNG: normal FBG during the whole pregnancy, ENG: normal FBG in the early stage (T1) of pregnancy, LNG: normal FBG in the late stage (T3) of pregnancy, WHG: high FBG during the whole pregnancy

Fig. 4

Differentially abundant taxa of gut microbiota with dynamic changes in blood lipids across the three trimesters. There were significant differences by linear discrimination analysis effect size (LEfSe) analysis between DL1 and DL2 groups in the first trimester (T1, A), the second trimester (T2, B) and the third trimester (T3, C), between DL1 and DL3 groups in T1 (D), T2 (E) and T3 (F), between DL2 and DL3 groups in T1 (G), T2 (H) and T3 (I). DL3: with dyslipidemia only in T3, DL2: with dyslipidemia since T2, DL1: dyslipidemia starting from T1 of pregnancy

Fig. 5

Dynamic changes in the relative abundances of gut bacteria with the dynamic alterations in FBG and serum lipid levels across three trimesters. The different shaped dots represent the median (A–C, E–G) or the average relative abundance (D) of the gut bacteria in those groups with different onset time of high FBG or dyslipidemia in each trimester. A*: WHG > WNG in T1, P = 0.04. B*: LNG > WNG in T1, P = 0.038. C*: WHG > ENG in T2, P = 0.018. D*: ENG > WHG in T2, P = 0.048. E*: DL1 > DL2 and DL3 in T1, P = 0.022 and 0.021, respectively. F*: DL1 > DL2 and DL3 in T1, P = 0.011 and 0.003, respectively. G*: DL1 > DL2 in T1, P = 0.007. T1: the first trimester; T2: the second trimester; T3: the third trimester; WNG: normal FBG during the whole pregnancy, ENG: normal FBG in the early stage (T1) of pregnancy, LNG: normal FBG in the late stage (T3) of pregnancy, WHG: high FBG during the whole pregnancy; DL3: with dyslipidemia only in T3, DL2: with dyslipidemia since T2, DL1: dyslipidemia starting from T1 of pregnancy