Root causes of long-term complications of gestational diabetes mellitus: metabolic disturbances of the host and gut microbiota

Gestational diabetes mellitus (GDM) poses a risk of short-term and long-term complications for both mother and fetus. However, there is a lack of consensus on the screening approach and pathophysiology of GDM. Women were screened at 24 to 28 weeks gestation using the one-step screening approach and serum samples were collected for metabolomics based on 1H-NMR spectroscopy. A random forest classifier was developed to evaluate its diagnostic efficacy on GDM. Serum metabolic fingerprints of women with GDM differed significantly from those with normoglycemic. Of the 59 differential metabolites identified, 25 were well-known risk metabolites associated with type 2 diabetes or cardiovascular diseases, such as branched-chain amino acids and trimethylamine N-oxide. In addition, most of the differential metabolites were microbial metabolites or could be metabolized by gut microbes. The correlation between serum metabolites and maternal 75 g OGTT glucose values supported the establishment of a random forest classifier, which selected 21 metabolites to predict GDM with an AUC of 0.988. Metabolic disturbances in the host and gut microbiota may be a persistent contributor to the risk of developing type 2 diabetes or cardiovascular diseases in GDM. Targeting microbiota is one intervention that needs to be considered.