The Gut Microbiome Dynamically Associates with Host Glucose Metabolism throughout Pregnancy: Longitudinal Findings from a Matched Case‐Control Study of Gestational Diabetes Mellitus

Abstract

Though gut microbiome disturbance may be involved in the etiology of gestational diabetes mellitus (GDM), data on the gut microbiome's dynamic change during pregnancy and associations with gestational glucose metabolism are still inadequate. In this prospective study comprising 120 pairs of GDM patients and matched pregnant controls, a decrease in the diversity of gut microbial species and changes in the microbial community composition with advancing gestation are found in controls, while no such trends are observed in GDM patients. Multivariable analysis identifies 10 GDM-related species (e.g., Alistipes putredinis), and the integrated associations of these species with glycemic traits are modified by habitual intake of fiber-rich plant foods. In addition, the microbial metabolic potentials related to fiber fermentation (e.g., mannan degradation pathways) and their key enzymes consistently emerge as associated with both GDM status and glycemic traits. Microbial features especially those involved in fiber fermentation, provide an incremental predictive value in a prediction model with established risk factors of GDM. These data suggest that the gut microbiome remodeling with advancing gestation is different in GDM patients compared with controls, and dietary fiber fermentation contributes to the influence of gut microbiome on gestational glycemic regulation.

Microbiome in Female Reproductive Health: Implications for Fertility and Assisted Reproductive Technologies

“…A high-fiber diet is believed to increase SCFA levels and improve human health [ 66 ]. A recent study involving 120 pairs of GDM women and matched controls from the first trimester to the third trimester indicated that the healthy status of women suffering from GDM was modified with the intake of a high-fiber diet [ 25 ]. Parallel changes in the gut microbiome, including Escherichia coli , Fusobacterium mortiferum , Bacteroides massiliensis , and Bifidobacterium dentium , were also observed [ 25 ].…”

“…Studies indicated that the increase of Enterobacteriaceae, Streptococcus , and Lactobacillus , as well as high levels of insulin insensitivity and blood glucose, helps mothers harvest more energy, thus supporting the growth of fetuses [ 172 , 177 ]. Nevertheless, an unhealthy lifestyle during pregnancy disturbs the maternal microbiome, which is associated with poor maternal conditions and leads to the occurrence of pregnancy complications, further influencing the development of infants [ 13 , 25 , 26 , 175 ].…”

“…With current knowledge and case-control studies, bacterial biomarkers can be identified to promote the prevention and early diagnosis of many pregnancy complications. Previous studies have associated the microbiomes in the female gut and reproductive tract with some obstetric and gynecological diseases, such as recurrent miscarriage (RM) [ 179 ], repeat implantation failure (RIF) [ 22 , 134 , 146 , 148 , 180 ], PCOS [ 29 , 181–192 ], GDM [ 25 , 175 , 193–199 ], gestational hypertension [ 200 ], PE [ 27 , 201–209 ], preterm labor, and preterm premature rupture of membrane (PPROM) [ 26 , 210–214 ]. While some studies reported consistent observations for certain diseases, other studies reached controversial conclusions.…”

“…Differences in ethnicity and environments can be one of the reasons that result in such controversial observations, while further associations remain explored. A prospective study conducted by Sun et al demonstrated significant differences in the gut microbiome, including Ruminococcus bromii , Alistipes putredinis , and Bacteroides ovatus , between GDM women and their healthy controls [ 25 ]. Furthermore, they indicated that the microbial characteristics at early pregnancy can be used to predict the occurrence of GDM in the future [ 25 ].…”

“…Pregnancy is a complex process during which several critical changes occur in a woman’s body, including alterations in immune response, hormonal balance, microbial pattern, and metabolism, to support or adapt to the growth and development of the fetus in the uterus [ 9 , 11 , 24 ]. If these dynamic patterns during pregnancy are disrupted, it can lead to a variety of pregnancy complications such as gestational diabetes mellitus (GDM), preeclampsia (PE), and adverse pregnancy outcomes including premature labor, low birth weight, and macrosomia [ 25–28 ]. For example, many studies have confirmed a close association between unfavorable maternal health and the perturbation of metabolites originating from disrupted microbiota during pregnancy [ 29 ].…”