Offspring of mothers who consume diets rich in fats and sugars while pregnant or breastfeeding are at heightened risk for fatty liver disease in later years. Recent research conducted at the University of Oklahoma indicates that this vulnerability could be significantly reduced. Specifically, the experiment involved administering a natural substance produced by healthy intestinal bacteria to pregnant and lactating mice, resulting in their young exhibiting substantially decreased incidence of fatty liver disease as they matured.
This key substance, known as indole, is generated by advantageous gut microbes during the metabolism of tryptophan, an essential amino acid present in various foods such as turkey, nuts, and seeds. These discoveries contribute to the expanding body of evidence aimed at averting metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent type of fatty liver condition that impacts individuals across all ages. Notably, MASLD tends to progress more rapidly in pediatric populations and maintains a strong association with diabetes mellitus.
“Around 30% of obese children suffer from MASLD, while approximately 10% of non-obese children are affected,” explained Jed Friedman, Ph.D., who serves as director of the OU Health Harold Hamm Diabetes Center and holds a professorship in biochemistry and physiology at the OU College of Medicine. “The danger escalates further when the mother carries excess weight or adheres to an unhealthy eating regimen. In young patients, this condition remains asymptomatic for extended periods and is frequently only identified after parents consult medical professionals regarding liver-specific complaints.”
Examining the Influence of the Gut Microbiome
Jed Friedman spearheaded the investigation in collaboration with Karen Jonscher, Ph.D., an associate professor of biochemistry and physiology within the OU College of Medicine. Their comprehensive findings appeared in the esteemed journal eBioMedicine. The research group sought to determine the extent to which the collective community of gut bacteria, referred to as the microbiome, modulates the onset and severity of fatty liver disease.
In their experimental design, female mice were maintained on a Western-style diet characterized by elevated levels of fat and sugar from conception through the lactation phase. A subset of these mice was supplemented with indole. Following weaning, the resulting offspring transitioned to a balanced standard chow, which was subsequently altered to the Western-style diet to provoke the emergence of fatty liver pathology.
“Since newborns acquire their initial microbiome primarily from their mothers, suboptimal maternal nutrition can detrimentally alter the child’s microbial composition from the outset,” noted Friedman.
Enhanced Liver Function and Enduring Protective Effects
The progeny of mothers treated with indole demonstrated a range of superior health outcomes. Their livers remained in better condition, they accumulated less body weight, exhibited more stable blood glucose concentrations, and formed smaller adipocytes, even following prolonged exposure to detrimental dietary patterns in adulthood. Additionally, the scientists detected heightened activity in a safeguarding intestinal mechanism mediated by the aryl hydrocarbon receptor (AHR).
Analysis revealed no elevation in deleterious hepatic lipids termed long-chain ceramides, whereas concentrations of protective very long-chain ceramides increased notably. In a pivotal follow-up procedure, fecal microbiota harvested from the safeguarded offspring were transplanted into recipient mice lacking prior indole exposure. These recipients likewise displayed diminished liver impairment, solidly affirming the microbiome’s pivotal role in conferring protection.
Potential Strategies for Mitigating Pediatric MASLD
While this study utilized animal models and direct translation to human applications remains premature, the outcomes illuminate promising avenues for curbing the escalating burden of MASLD via proactive interventions during critical developmental windows.
Currently, achieving weight reduction stands as the sole validated therapeutic approach for established pediatric MASLD, with no pharmacotherapies gaining regulatory approval to date. “Enhancing the maternal gut microbiome through targeted means could substantially diminish the likelihood of MASLD onset in children,” emphasized Jonscher. “Such preventive measures offer a superior alternative to attempting disease reversal after significant advancement has occurred.”
This research underscores the profound interplay between maternal diet, microbial ecology, and offspring metabolic health, paving the way for innovative, non-invasive strategies to safeguard future generations against this pervasive liver disorder. By focusing on modifiable factors like gut bacterial metabolites, scientists aim to interrupt the cycle of diet-induced metabolic diseases before they take hold.
