Microbial enterotype is linked to episodic and working memories via brain function in the parietal and occipital cortices

Classification of human gut microbiome into distinct enterotypes based on gut microbial community composition has provided an attractive framework for population stratification. While empirical evidence indicates that microbial enterotype is related to brain function and memory, the neural processes underlying this interaction remain to be further characterized. In 510 healthy young adults, we used 16S rDNA amplicon sequencing to perform enterotyping, acquired resting-state functional MRI data to calculate brain functional measures, and assessed both episodic and working memories. Inter-enterotype differences in brain functional measures were examined, followed by performance of correlation and mediation analyses to disentangle the potential associations between enterotype, brain function, and memory. We found significant differences in multiple brain functional measures in the parietal and occipital cortices across Bacteroides, Prevotella, and Ruminococcaceae enterotypes. Moreover, these differential brain functional measures were correlated with both episodic and working memories, and further mediated the relationship between enterotype and memory. Our findings not only establish brain function as the mediating factor between enterotype and memory, but also hold translational potential for informing novel treatment for cognitive dysfunction via targeting the microbiota-gut-brain axis.