University of Oklahoma Study: Indole Compound May Reduce Fatty Liver Risk in Offspring
A study from the University of Oklahoma indicates that children born to mothers consuming diets high in fat and sugar during pregnancy and breastfeeding may have an elevated risk of developing fatty liver disease later in life. The research suggests this risk could be mitigated.
A naturally occurring compound named indole, produced by healthy gut bacteria, was administered to pregnant and nursing mice. Their offspring subsequently showed reduced rates of fatty liver disease as they aged.
Indole is generated when beneficial gut bacteria break down tryptophan, an amino acid found in foods such as turkey and nuts.
Addressing MASLD: A Growing Concern
These findings contribute to ongoing research focused on preventing Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), which affects both adults and children. MASLD often progresses more rapidly in children and is closely linked to diabetes.
Dr. Jed Friedman, director of the OU Health Harold Hamm Diabetes Center, provided context on its prevalence: "MASLD prevalence is approximately 30% in children with obesity and about 10% in children without obesity." He also noted that the risk is higher with maternal obesity or a poor diet.
The OU Research: Unpacking Microbiome Influence
The study, led by Dr. Friedman and Dr. Karen Jonscher, was published in the journal eBioMedicine. The team investigated the influence of the gut microbiome on fatty liver disease development.
In the experiment, female mice were fed a high-fat, high-sugar (Western-style) diet during pregnancy and lactation; some of these mice also received indole supplementation. After weaning, offspring were initially given a standard diet, later transitioning to a Western-style diet to encourage fatty liver disease development. Dr. Friedman explained that a maternal diet can negatively influence the infant's microbiome, as "offspring inherit their microbiome from their mother."
Indole's Protective Effects on Offspring Health
Offspring from mothers supplemented with indole exhibited several positive health outcomes, even when later exposed to an unhealthy diet:
- They demonstrated healthier livers.
- They gained less weight and maintained lower blood sugar levels.
- They developed smaller fat cells.
Researchers also observed the activation of a protective gut pathway involving the acyl hydrocarbon receptor (AHR). The study reported no increase in harmful long-chain ceramides in the liver, while levels of beneficial very long-chain ceramides increased.
In a key experiment, the protective role of the microbiome was further reinforced: transferring gut bacteria from the protected offspring to other mice that had not received indole also resulted in reduced liver damage.
Towards Early Prevention of MASLD in Humans
While this research was conducted in animals and is not yet directly applicable to humans, the findings suggest new approaches for reducing the impact of MASLD through early prevention.
Dr. Jonscher stated that "weight loss is currently the only effective treatment for pediatric MASLD once established, with no approved medications." She added that improving the mother's microbiome could potentially help prevent MASLD development in offspring, which would be preferable to managing the disease once it has progressed.