When mothers eat a diet high in fat and sugars, their unborn babies can develop liver stress that continues into early life. A new study published in the journal Liver International sheds light on changes to the fetus’s bile acid, which affects how liver disease develops and progresses.

Bile acids typically help with digestion and absorb dietary fats in the small intestine, but when they reach excessive levels, they become toxic and can damage the liver. While the mother can detoxify the acids, the fetus lacks that ability. Bile acids may re-circulate to the mother for detoxification, but if they don’t, they build up in the fetal liver, setting the stage for future problems.

The findings suggest that early exposure to excess bile acids in the womb may be one important factor underlying the early development of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects up to 30% of youth.

“It’s a huge public health concern, as we know mothers with obesity or those eating a poor diet can predispose the next generation to a risk for obesity, diabetes and other metabolic diseases beginning in the womb, thus completing a vicious cycle from mother to infant,” said Jed Friedman, Ph.D., associate vice provost for diabetes programs at the University of Oklahoma Health Sciences and director of OU Health Harold Hamm Diabetes Center. Friedman was co-senior author of the study with Stephanie Wesolowski, Ph.D., of the University of Colorado Anschutz Medical Campus.

By the time the offspring studied were juveniles, they had liver damage, including increased amounts of a protein called collagen, which is linked to fibrosis (a build-up of scar tissue), and activated liver cells involved in fibrosis. The high-fat diet also led to changes in how some liver genes worked, particularly those related to bile acid processing. These changes persisted regardless of what the offspring ate after being weaned.

In addition, offspring whose mothers ate a high-fat diet had more bile duct cells (cells that drain bile from the liver), suggesting the liver was trying to compensate for damage.

“This study provides evidence that MASLD originates in the womb, influenced at least in part by a mother’s high-fat diet,” Friedman said. “The discovery of elevated bile acid levels in fetuses may provide insights into the early stages of MASLD and its progression before it worsens.

“A mother’s diet during pregnancy plays a powerful role in shaping her baby’s future health. By making healthy food choices, moms can help lower their child’s risk of developing metabolic diseases like MASLD later in life.”

###

About the Project

The research paper in Liver International can be found here. The work was supported by NIH grants R24-DK090964, R01-DK128416, F30-DK122672, R01-DK108910, P30-DK048520, P51-OD011092, P30-NS048154 and P30-DK116073.