Microbiota, a source of early markers for gestational diabetes

Diabetes

The microbiota of women suffering from gestational diabetes has a very specific signature from the first trimester. This signature may be involved in the pathogenesis of the disorder, thus opening the door to more efficient diagnostic tools that detect the disease earlier.¹

Photo : Le microbiote, source de marqueurs précoces du diabète gestationnel

About this article

Created 05 April 2023

Updated 19 April 2023

Will it soon be possible to predict gestational diabetes (GDM) in the first trimester of pregnancy? So suggests a recent study published in the journal Gut.

Israeli researchers recruited 394 women aged between 18 and 40 who were less than 3 months pregnant. The researchers collected stool samples to analyze their microbiota and blood samples to measure parameters such as blood glucose and serum cytokines. The researchers also recorded the participants’ medical history and dietary habits.

The participants were then followed for 27 to 30 weeks. In the second trimester, 44 of them (11%) developed GDM.

Clear differences in women with gestational diabetes

The results of the blood analyses showed that, as early as the first trimester, women who developed GDM had glucose intolerance and high levels of cytokines, particularly of interleukin-6 (IL-6), unlike the women without GDM. Several studies have shown that, by promoting inflammation, IL-6 is involved in various forms of diabetes, including GDM.

The analysis of the gut microbiota showed that as early as the first trimester women with GDM also presented:

A decrease in short-chain fatty acids (SCFAs), especially isovalerate and isoburate, which are known to improve insulin sensitivity and lower inflammatory responses;
A lower abundance of Prevotella, whose presence is associated with improved glucose metabolism;
An enrichment of certain metabolic pathways, such as mevalonate, which is associated with increased IL-6 levels.

Symptoms reproduced in mice through microbiota transplant

To find out whether these characteristics play a role in the pathogenesis of GDM, the researchers then transplanted the fecal microbiota (FMT) of the women in the study into germ-free mice (lacking microbiota).

They observed the same symptoms in the FMT mice as in the women with GDM: glucose intolerance and higher levels of IL-6. This suggests that the microbiota may be involved in the pathogenesis of GDM.

The results were the same for FMTs from pregnant women in two other cohorts from Finland and the US, suggesting the “universal” nature of the microbiota changes associated with GDM.

A global public health issue

Obesity has been on the rise in many countries since the mid-1970s, with excess weight being a major risk factor for gestational diabetes. The obesity “epidemic” has thus seen an increase in the number of women affected by this glucose metabolism disorder, as well as an increase in perinatal complications.

Today, on average, 10% of pregnant women are affected by gestational diabetes.
According to a meta-analysis published in 2022, the highest prevalences of gestational diabetes are found in North Africa and the Middle East (27.6%);
and in Southeast Asia (20.8%).
The lowest prevalences are in North America and the Caribbean (7.1%);
and in Europe (7.8%).²

Towards new detection tools?

The researchers then used a prediction model to see which first trimester data (microbiome composition, cytokine profile, medical history, or dietary characteristics) most accurately predicted GDM. The results indicated that the model incorporating the medical record was the most accurate (odds ratio – OR – = 3.2), followed by the model based on the fecal microbiota. Using both models together, the OR increased to 4.
Although further studies are needed to determine whether dysbiosis is caused by diabetes or vice versa, these results suggest it may be possible to manage GDM from an earlier stage and, more importantly, to mitigate the adverse effects of the disorder on the health of mother and child.