April 19, 2023 | An international team of researchers has found that gut microbes can help diagnose gestational diabetes mellitus (GDM) as early as the first trimester of pregnancy, months earlier than is happening currently. But the long-term aim of the group is “not to diagnose and treat, but to predict and prevent” one of the most common pregnancy-related medical complications with adverse health implications for mother and child, according to Omry Koren, Ph.D., a microbiology professor at Bar-Ilan University (Israel) who led the study.
Metabolic and inflammatory markers are also on the panel—notably, elevated levels of serum cytokines and low levels of short-chain fatty acids, the end product of fermentation in the gut—as well as information from the medical records of the women, says first author Yishay Pinto, currently a postdoctoral fellow in the Stanford University School of Medicine. The study, which published recently in Gut (DOI: 10.1136/gutjnl-2022-328406), additionally found that the gut microbiome may play a role in mediating disease development, given that the diabetes phenotype could be transferred from the feces of affected women to germ-free mice.
GDM is a condition where women without diabetes develop glucose intolerance during pregnancy. About 10% of pregnant women worldwide are plagued by the condition, the researchers say. It is currently managed largely by lifestyle modification, but in the future may be treated with pre, pro, and postbiotic supplements.
Researchers elsewhere have tried to develop predictive tests for GDM based on fetal metabolites, blood biomarkers, and clinical records, says Pinto. But this is likely the first time the microbiome has been used for this purpose. The beauty of the approach is that the gut is readily amenable to intervention, unlike treatments for risk factors such as being overweight or obese.
Koren was part of the first group to study the microbiome in healthy pregnancy a decade ago as a postdoc at Cornell University. When he returned to Israel to open a new lab, he decided to investigate the known connection between diabetes and the microbiome—but specifically in the context of pregnancy.
In the first part of the latest experiment, Koren and his team took fecal and serum samples from a cohort of pregnant Israeli women in their first trimester to characterize their microbiota, metabolite, inflammation, and hormone profiles, as well as document their lifestyle habits and medical history, he says. This was used to build a machine learning model to predict which women would develop GDM.
The prediction model was validated using published data on a patient cohort in China, Koren adds, and the fecal microbiota transplant was done from cohorts in Israel, America, and Finland. This pointed to the generalizability of the model to women irrespective of their genetics, diet, and geography.
Much larger clinical studies are now being planned in Israel and the U.S. that will involve some sort of dietary or behavioral intervention to see if it changes the microbiome of women such that they reduce their risk of developing the condition, Koren says. Pregnant women overall tend to be more committed to research than the general population because of worries about the fetus as well as their own health, he adds.
Earlier diagnosis could translate into prevention of related health problems for mothers and their babies, including the development of type 2 diabetes later, says Pinto. GDM also puts babies at higher risk of being born very large and arriving early, and thus more often needing to be delivered by cesarean section.
“Gestational diabetes is just the beginning,” concurs Koren, since it affects life long after pregnancy. Prevention of GDM means a lower risk of multiple health problems that include postpartum depression in mothers and obesity in their offspring.