Study Finds Grandmaternal High-fat Diet can Impair Social Behavior in Descendants

What a grandmother ate can affect a grandchild’s brain development according to a new study performed on mice.

New research from investigators at the University of Texas Medical Branch finds that adverse effects of maternal high-fat diet on brain development and related disorders, including autism spectrum disorder, could carry over to a second generation of descendants. In essence, grandmaternal diets could impact brain development and behavior in their grandchildren. The study was published today in Cell Reports.

 “Our study focused on the impact of high-fat diet exposure in the maternal lineage on behavioral outcomes associated with neurodevelopmental disorders in descendant generations,” said Shelly A. Buffington, assistant professor in the Department of Neurobiology and faculty in the Sealy Center for Microbiome Research at UTMB. “Remarkably, we found that a high fat grandmaternal diet has the potential to impact neurodevelopment and long-term behavioral outcomes across multiple descendant generations.”

This new study builds on findings from Buffington’s previous study demonstrating the effects of maternal high-fat diet on offspring brain plasticity and social behavior published in Cell in 2016.

In the current study, researchers compared gut microbial richness across three generations of mice in which only the grandmaternal mice were fed either a control or high-fat diet. Diet-driven loss of microbial richness observed in the grandmaternal females, and their first-generation offspring was partially recovered by the second descendant generation, yet social deficits akin to those in the first descendant generation remained evident in the second.

“These data suggested that disruption of the maternal gut microbiome, instead of that of the juvenile offspring, could be the culprit underlying abnormal social behavior in the descendant generations,” said study co-first author and recent UTMB Neuroscience Graduate Program doctoral graduate, Claudia Di Gesù.

“This study identifies a critical link between grandmaternal high-fat diet, stability of descendant microbial communities in response to environmental pressures, and maladaptive behaviors, with profound implications for both host disease susceptibility and therapeutic targeting of the gut microbiome,” said Buffington. “The discovery highlights the potential for therapeutic targeting of the maternal gut microbiome to improve brain development and long-term behavioral outcomes across multiple generations of descendants.

In addition, Di Gesù suggests that preconception, prenatal, and postnatal supplementation with probiotics could one day be incorporated into a comprehensive regimen. A regimen including micronutrient, folic acid, and vitamin D dietary supplementation, physical activity, and cognitive behavior approaches to help improve long-term health outcomes in both the mother and her child, and, potentially, her children’s children.

Other UTMB co-authors include former Buffington Lab postdoctoral scholar Robert Fultz and research associate Ian Bolding. Researchers from Baylor College of Medicine and the University of Palermo also contributed to this study.

The work was supported by funding from the National Institutes of Health, the Brain & Behavior Research Foundation, the Scott-Gentle Foundation, the Gulf Coast Center for Precision Environmental Health, and the UTMB Institute for Human Infections and Immunity.