A mother’s diet during pregnancy and breastfeeding may have a profound and lasting impact on her child’s liver health, new research suggests. Scientists have discovered that a naturally occurring compound produced by healthy gut bacteria, called indole, can significantly reduce the risk of fatty liver disease in offspring, even when mothers consume a high-fat, high-sugar diet.
The findings, published in the journal eBioMedicine, offer a potential preventative strategy for metabolic dysfunction-associated steatotic liver disease (MASLD), a growing concern for both adults and children. MASLD, formerly known as non-alcoholic fatty liver disease (NAFLD), is often more aggressive in children and closely linked to the development of type 2 diabetes.
“The prevalence of MASLD is approximately 30% in obese children and approximately 10% in non-obese children,” explained Dr. Jed Friedman, professor of biochemistry and physiology at the University of Oklahoma School of Medicine and director of the OU Health Harold Hamm Diabetes Center. “If the mother is obese or has a poor diet, the risk increases further.” The disease often remains undetected until liver-related symptoms appear, highlighting the importance of preventative measures.
How Indole Protects the Liver
Researchers at the University of Oklahoma investigated the role of the gut microbiome in the development of fatty liver disease. They fed female mice a Western-style, high-fat, high-sugar diet throughout pregnancy and lactation. Some of these mice also received indole supplementation. After the pups were weaned, they were initially fed a normal diet before being reintroduced to the Western diet to induce fatty liver disease.
The results were striking. Pups born to mothers who received indole exhibited significantly healthier livers, experienced less weight gain, and had improved blood sugar control. Their fat cells were also smaller, and this protective effect persisted even after exposure to the unhealthy diet. The study identified a key mechanism: indole activates the aryl hydrocarbon receptor (AHR) in the gut.
This activation led to changes in the production of ceramides, a type of lipid. Specifically, the increase in harmful, long-chain ceramides—known to contribute to liver damage—was suppressed, while beneficial ultra-long-chain ceramides were increased. These ultra-long-chain ceramides appear to play a protective role in liver health.
The Power of the Maternal Microbiome
To further investigate the role of the gut microbiome, researchers performed fecal microbiota transplants (FMT). They transferred gut bacteria from the protective rat pups into other mice that had not received indole. Remarkably, these recipient mice also showed reduced liver damage, confirming that the gut microbiome itself is a critical factor in providing protection.
“Because children inherit their microbiome from their mothers, the mother’s diet has a direct impact on the formation of the infant’s intestinal environment,” Dr. Friedman explained. This suggests that optimizing the maternal microbiome could be a powerful strategy for preventing MASLD in children.
Indole and Tryptophan: A Dietary Connection
Indole is a natural metabolite produced when beneficial gut bacteria break down the amino acid tryptophan. Tryptophan is found in a variety of protein-rich foods, including turkey, chicken, eggs, salmon, tuna, tofu, beans, nuts like almonds and walnuts, and dairy products like cheese and milk. This highlights the importance of a balanced diet rich in tryptophan-containing foods during pregnancy and breastfeeding.
“Currently, there are no approved treatments for pediatric MASLD other than weight loss,” said Dr. Karen Johnsher, associate professor of medicine at the University of Oklahoma College of Medicine. “Strategies to improve the maternal microbiome may be a much more effective preventative approach than treating the disease after it has progressed.”
Indole’s benefits extend beyond liver health. It’s known to reduce inflammation in the intestinal mucosa, maintain metabolic balance, and regulate immune responses. This suggests that indole may have broader implications for overall health and well-being.
While this research was conducted in mice, the findings offer a promising avenue for preventing MASLD in children. Further research is needed to determine the optimal dosage of indole and to explore the potential for developing dietary interventions or probiotic supplements to enhance indole production in the gut. However, the current evidence strongly suggests that a mother’s diet plays a crucial role in shaping her child’s long-term liver health.
