Effects of insulin therapy on Gut Microbiota of Gestational Diabetes Mellitus (GDM) and their newborns

Abstract

Objective: There are about one-third of women with gestational diabetes mellitus (GDM) fail in their glycemic control following a diet modification. GDM has been associated with gut dysbiosis. However, the role of gut microbiota in GDM with insulin intervention remains unknown. In addition, the impact of gut dysbiosis in GDM mothers on their newborns is unclear. Here we compared the composition of gut microbiota in GDM women with and without insulin therapy before and after the intervention. The gut microbiota of their newborns was also analyzed. We also investigated the association between insulin therapy, maternal gut microbiota, and neonatal gut microbiota.

Methods: Seventy-one pregnant women were divided into the non-GDM group (n=33) and GDM group (n=38). All of the GDM participants were received dietary recommendations. During follow-up, 30 GDM women achieved glycemic control goals with dietary interventions, assigned to the GDM-D group. While 8 women with GDM received insulin intervention since dietary intervention did not achieve glycemic control goals, assigned to the GDM-I group. The blood and feces of the participants were obtained before the intervention (at the time of confimed GDM, 24 to 28 weeks of gestation) and after the intervention (at the time of before delivery, ≥37 weeks of gestation). The neonatal meconium (within 24 hours after birth) and first feces (within 48 hours after birth) were also collected.

Results: Blood glucose levels before the intervention were elevated in either GDM- D or GDM-I group when compared with those of the non-GDM group. However, the hyperglycemia before intervention was not different between GDM-D and GDM-I groups. Interestingly, the total cholesterol (TC) and low-density lipoprotein (LDL) levels were observed to be decreased in the GDM-I group than those of the GDM-D group before intervention. Meanwhile, no variations of triglycerides (TG) levels were observed among the tree groups before intervention. In terms of gut microbiota analysis, the proportion of Clostridiales, Lactobacillales, and Bacteroidetes before the intervention were elevated in the GDM-I group than those of the other two groups. On the other hand, no variations of gut microbiota were found in the GDM-D group before the intervention. when compared to the non-GDM group. After the intervention, blood glucose levels were decreased in both GDM-D and GDM-I groups but still elevated than those of the non- GDM group. The TC and LDL levels, which were previously decreased in GDM-I women before the intervention, were not statistically different from the other two groups after intervention. However, the triglycerides (TG) from before to after the intervention period were found to increase in both GDM-D and GDM-I groups, respectively. The elevations in Clostridiales, Lactobacillales, and Bacteroidetes were found to decrease to the normal levels in the GDM-I group after insulin intervention, respectively. In contrast, the elevation in Firmicutes/Bacteroidetes (F/B) ratio was observed in the GDM-D than those of the non-GDM and GDM-I counterparts. These increased F/B ratios were found only in newborns of the GDM-D mothers. Interestingly, the gut microbiota composition of mothers and newborns was found to correlate with the maternal glycemic and lipidic profiles. Conclusions: Early gut dysbiosis could be an indicator of insulin intervention in severe GDM women. The gut dysbiosis of the GDM mother could be attenuated by insulin intervention. The beneficial effect of insulin intervention on maternal gut microbiota can be transmitted to their newborns. Thus, may reduce the incidence of diabetes in the children of GDM mothers later in life. Insulin intervention may be considered as a preferred candidate for women with generalized GDM, based on its role in alleviating gut dysbiosis in GDM mothers and their offspring.