AUTHOR=Hammond Tyler C. , Green Stefan J. , Jacobs Yael , Chlipala George E. , Xing Xin , Heil Sally , Chen Anna , Aware Chetan , Flemister Abeoseh , Stromberg Arnold , Balchandani Priti , Lin Ai-Ling TITLE=Gut microbiome association with brain imaging markers, APOE genotype, calcium and vegetable intakes, and obesity in healthy aging adults JOURNAL=Frontiers in Aging Neuroscience VOLUME=Volume 15 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1227203 DOI=10.3389/fnagi.2023.1227203 ISSN=1663-4365 ABSTRACT=Advanced age is a significant factor in changes to brain physiology and cognitive functions. Recent research has highlighted the critical role of the gut microbiome in modulating brain functions during aging, which can be influenced by various factors such as apolipoprotein E (APOE) genetic variance, body mass index (BMI), diabetes, and dietary intake. However, the associations between the gut microbiome and these factors, as well as brain structural, vascular, and metabolic imaging markers, have not been well explored. In this study, we investigated the gut microbiome of 30 community dwelling older adults and found several important correlations. Individuals with APOE 2 and APOE 4 genotypes had distinct microbiota composition, and higher level of pro-inflammatory microbiota were associated higher BMI and diabetes. In contrast, calcium-and vegetable-rich diets were associated with microbiota that produced short chain fatty acids leading to an anti-inflammatory state. We also found that important gut microbial butyrate producers were correlated with the volume of the thalamus and corpus callosum, which are regions of the brain responsible for relaying and processing information. Additionally, putative proinflammatory species were negatively correlated with GABA production, an inhibitory neurotransmitter. Furthermore, we observed that the relative abundance of bacteria from the family Eggerthellacaeae, equol producers, was correlated with white matter integrity in tracts connecting the brain regions related to language, memory, and learning. These findings highlight the importance of gut microbiome association with brain health in aging population and could have important implications aimed at optimizing healthy brain aging through precision prebiotic, probiotic or dietary interventions.