(P25-020-24) The Impact of Maternal Diet and Ischemic Stroke on Untargeted Metabolomics Analysis in Stool Samples From Male and Female Mice

Objectives: Changes in levels of metabolites can be used to measure the alterations in the gut microbiota, which can be significant markers for the etiology of diseases. This project utilizes untargeted metabolomics analyses to discover and identify metabolism changes in response to maternal dietary deficiencies in one-carbon metabolism and stroke outcome.

Methods: Adult female mice were fed on either control (CD), folic acid (FADD), or choline deficient diet (ChDD) four weeks prior to pregnancy, during pregnancy, and lactation. Male and female offspring were weaned on to a CD. At 2 months of age, the offspring were subjected to ischemic stroke. Stool samples were collected from offspring prior to ischemic stroke, and 1 and 4 weeks post-ischemic stroke. Stool samples underwent untargeted metabolomic analysis and data were analyzed using R and MetaboAnalyst.

Results: Prior to stroke there were no changes in metabolites between experimental groups. There were both sex and maternal dietary differences noted in metabolites at 1- and 4-week post-stroke timepoints. At the 1-week post-stroke, female mice, especially on FADD had more changes in metabolites than males. Abnormal levels of metabolites that are involved in neuroprotective mechanisms during neurodevelopment in early age, immune function, and fatty acid mechanisms. Comparatively, at the 4-week post-stroke timepoint, female mice on either FADD or ChDD maternal diet had more metabolite changes. There were more changes in metabolites after 4 weeks after ischemic stroke compared to 1-week. The abnormal metabolite levels suggest significant molecular abnormality and inflammation in the brain and gut because of maternal diet in early life and ischemic stroke.

Conclusions: This untargeted metabolomics experiment allows us to see a broad spectrum of detrimental effects of maternal diet deficiencies in one-carbon metabolism and stroke in adult female and male mice, although our data suggest that females are more affected. Further research is required to elucidate the mechanism and their specific effects in later life. This study has demonstrated a long-lasting impact of maternal dietary deficiencies on central nervous system and gut microbiome inflammation after ischemic stroke.

Funding Sources: American Heart Foundation