Microbial Metabolites for Promoting Brain Health (UCLA Case No. 2024-196)

UCLA researchers in the Department of Integrative Biology and Physiology have developed a maternal supplementation with microbiome-dependent metabolites to promote growth and neurobehavioral health in children impacted by maternal protein undernutrition.

BACKGROUND: Protein undernutrition poses a significant risk of childhood stunting, accompanying enduring neurological issues. The gestational period is a critical developmental stage, during which deficiency in maternal protein intake can cause cognitive impairment and anxiety in adult offspring. Human and animal studies have shown that abnormalities in the gut microbiome contribute to the stunting caused by malnutrition. Consequently, microbiome-based treatments hold promise for addressing malnutrition-induced growth defects. However, existing therapies for treating childhood stunting often fail to alleviate the associated neurobehavioral impairments, highlighting an unmet need for developing microbiome-based interventions to ameliorate the neurological comorbidities.

INNOVATION: UCLA researchers have discovered that modifying the maternal microbiome can mitigate adverse neurobehavioral outcomes in offspring caused by maternal protein undernutrition. They have developed a maternal supplementation consisting of 10 diet and microbiome-dependent metabolites that can be administered during pregnancy to reduce the risk of abnormal brain and behavioral development in offspring. In mouse models, the metabolite cocktail was shown to be highly effective in preventing anxiety-like and cognitive behavior impairments in the long-term compared to nutrition support alone. As malnutrition continues to be a global health burden, this microbial-centered intervention can be critical to address malnutrition-associated neurobehavioral disorders.

POTENTIAL APPLICATIONS:

• Maternal supplementation that regulates the microbiome in response to dietary protein restriction
• Ameliorating neurological disorders in malnourished children

ADVANTAGES:

• Supporting sustained microbial rehabilitation to prevent neurobehavioral and cognitive impairments in infancy and adult life
• Addresses co-morbid neurobehavioral disorders induced by malnutrition not amenable to current malnutrition interventions

DEVELOPMENT-TO-DATE: Successful demonstration of invention in cross-fostering mouse model.

Related papers:

Coley, E., Lum, G., Pronovost, G., Ozcan, E., Yu, K., Mcdermott, J., ... & Hsiao, E. Y. (2024). The maternal microbiome modifies adverse effects of protein undernutrition on offspring neurobehavioral impairment in mice. bioRxiv, 2024-02.

Keywords: Protein undernutrition, malnutrition, stunting, growth defects, microbial metabolites, microbiome, neurobehavioral impairment, brain health, neurodevelopment, maternal supplementation