Researchers at the University of Oklahoma have discovered that a compound produced by healthy gut bacteria can reduce the risk of fatty liver disease in the offspring of mice fed a high-fat, high-sugar diet during pregnancy and nursing. The compound, indole, derived from breaking down the amino acid tryptophan, improved liver health, blood sugar levels, and weight management in the young mice. This finding highlights the role of the maternal microbiome in preventing metabolic disorders like MASLD in children.
Children of mothers who consume diets high in fat and sugar during pregnancy and breastfeeding are at increased risk for metabolic dysfunction-associated steatotic liver disease (MASLD) later in life. A new study from the University of Oklahoma reveals a potential preventive measure through the gut microbiome. Led by Jed Friedman, Ph.D., director of the OU Health Harold Hamm Diabetes Center, and Karen Jonscher, Ph.D., both associate professors in the OU College of Medicine, the research was published in eBioMedicine.
The team investigated the impact of indole, a natural compound generated by beneficial gut bacteria when they metabolize tryptophan—an amino acid present in foods such as turkey and nuts. Female mice were given a Western-style high-fat, high-sugar diet throughout pregnancy and lactation, with some supplemented with indole. After weaning, the offspring were initially on a standard diet and later switched to the unhealthy Western diet to induce fatty liver disease.
Offspring from mothers receiving indole exhibited significant benefits: healthier livers with reduced fatty buildup, lower weight gain, stable blood sugar, and smaller fat cells, even under the poor diet. The study noted no rise in harmful long-chain ceramides in the liver, alongside increased beneficial very long-chain ceramides. Activation of the protective aryl hydrocarbon receptor (AHR) pathway in the gut was observed, contributing to these effects.
Further evidence came from transferring gut bacteria from protected offspring to others, which similarly lessened liver damage, underscoring the microbiome's protective influence. Friedman explained the stakes: "The prevalence of MASLD in children is about 30% in those with obesity and about 10% in children without obesity. Unfortunately, the risk is higher if a mother is obese or consumes a poor diet."
MASLD affects both adults and children, progressing faster in the young and linking closely to diabetes. Currently, weight loss remains the sole treatment for established pediatric cases, with no approved drugs. Jonscher emphasized prevention: "Anything we can do to improve the mother's microbiome may help prevent the development of MASLD in the offspring. That would be far better than trying to reverse the disease once it has already progressed."
While conducted in mice, the results suggest avenues for human interventions targeting maternal gut health to curb rising childhood obesity-related liver issues.
