Human Fetus in Womb showing placenta to represent placental health issues
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Microbiome-related biomarkers that could predict three common and dangerous pregnancy complications have been identified by researchers at Ningbo University, China. They studied these markers in pre-eclampsia, gestational diabetes, and a liver condition called intrahepatic cholestasis. All three conditions are dangerous. Early diagnosis and treatment are key to preventing poor outcomes and lifelong consequences. The biomarkers included isobutyric, isovaleric, acetic, and propionic acid, which are all the short-chain fatty acids.

The study was published today in Frontiers in Cellular and Infection Microbiology.

New ways of predicting pregnancy complications are being intensely studied. One recent report found that RNA sequencing of amniotic fluid might provide important insights. Another suggested combining optical measures with ultrasound to improve pregnancy monitoring.

The causes of the three conditions looked at in this study are not fully understood, but a team led by Siqian Chen, at the Affiliated Hospital of Medical School, looked at whether specific changes in the microbiome could be used as biomarkers for these complications. In specific, they examined levels of short-chain fatty acids, metabolites which are produced following the fermentation of microbiota.

“This is the first retrospective study that links short-chain fatty acids to the risks of three types of pregnancy complications,” said Rongrong Xuan, senior author of the study. “It lays a foundation for the prevention of pregnancy-related diseases in the future.”

The team recruited 112 women who were divided into four groups: those who experienced healthy pregnancies, and those who were diagnosed with pre-eclampsia, gestational diabetes, or intrahepatic cholestasis. They excluded patients who had previously been diagnosed with diabetes or related medical conditions, had any other gastrointestinal symptoms, or were taking medication that might affect the gut microbiome. The team took medical histories and samples of blood that were analyzed for levels of several short-chain fatty acids.

“We analyzed and correlated the distribution of short-chain fatty acids during normal pregnancy and during three specific types of complicated pregnancy, gestational diabetes, pre-eclampsia, and intrahepatic cholestasis,” said Xuan. “The metabolic products of intestinal flora, short-chain fatty acids, during pregnancy are closely related to these pregnancy complications. They can be used as potential markers of pregnancy complications.”

He added that, “We used targeted metabolomics to carry out an analysis of serum short-chain fatty acids of pregnant women with gestational diabetes, pre-eclampsia, and intrahepatic cholestasis, and matched healthy control women.”

They found several strong candidates among the short-chain fatty acids for biomarkers, particularly isobutyric acid. All three groups of women who experienced these complications showed elevated levels of isobutyric acid. Patients with gestational diabetes and pre-eclampsia also had elevated levels of isovaleric, acetic, and propionic acid—the latter two potentially because of dyslipidemia.

By contrast, women diagnosed with intrahepatic cholestasis had much lower levels of all the short-chain fatty acids except isobutyric acid, and their levels of hexanoic acid correlated strongly with their illness. The team suggested that the lower levels of short-chain fatty acids in general might be due to lower abundance of flora in the gut microbiome, while the hexanoic acid may be linked to related inflammation.

The authors note that gestational diabetes, pre-eclampsia, and intrahepatic cholestasis are responsible for significant morbidity and mortality, with their prevalence varying from 7.5% to 27.0% in different regions, mainly depending on ethnicities and diagnostic criteria. Being able to detect these conditions early could save lives.

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