Maternal Gut Compound Shows Promise in Preventing Childhood Liver Disease

A naturally occurring compound produced by healthy gut bacteria, called indole, may hold the key to preventing metabolic dysfunction-associated steatotic liver disease (MASLD) in children, according to new research from the University of Oklahoma.

The Link Between Maternal Diet and Child Liver Health

Children born to mothers who consume a high-fat, high-sugar diet during pregnancy and breastfeeding are at increased risk of developing fatty liver disease later in life. MASLD, whereas affecting both adults and children, tends to progress more rapidly in children and is strongly linked with diabetes. Approximately 30% of obese children and 10% of non-obese children are affected by MASLD, often remaining undiagnosed until liver-related symptoms appear ¹.

How Indole Offers Protection

Researchers at the University of Oklahoma discovered that supplementing pregnant and lactating mice with indole significantly lowered rates of fatty liver disease in their offspring as they aged. Indole is created when healthy gut bacteria break down tryptophan, an amino acid found in foods like turkey and nuts ¹. The study, published in the journal eBioMedicine, demonstrated that indole not only protected the liver but also reduced weight gain and improved blood sugar levels in the young mice, even after exposure to an unhealthy diet ², ³.

The Role of the Gut Microbiome and AHR Signaling

The research suggests that the maternal microbiome plays a crucial role in preventing fatty liver disease. Maternal supplementation with indole or indole-3-acetic acid (I3A) activated aryl hydrocarbon receptor (AHR) signaling in the gut and liver of offspring ². This activation led to changes in gene expression, including increased levels of very long-chain ceramides, which have anti-fibrotic effects ². Fecal microbiota transfer (FMT) from offspring exposed to indole also protected recipient mice from liver damage ².

Implications for Prevention

These findings highlight the potential for modifying the microbiome as a preventative strategy against MASLD, rather than solely focusing on treatment after the disease develops. The study suggests that a mother’s diet during pregnancy and breastfeeding can have a lasting impact on a child’s liver health and that interventions targeting the gut microbiome could offer a new avenue for improving long-term health outcomes ¹.

“The disease in children is silent and typically isn’t discovered until a parent seeks help for their child for liver-related symptoms,” said Jed Friedman, Ph.D., director of the OU Health Harold Hamm Diabetes Center and professor of biochemistry and physiology in the OU College of Medicine ¹.