The gut microbiome has been linked to fear extinction learning in animal models. Here,
we aimed to explore the gut microbiome and memory domains according to obesity status.
A specific microbiome profile associated with short-term memory, working memory, and
the volume of the hippocampus and frontal regions of the brain differentially in human
subjects with and without obesity. Plasma and fecal levels of aromatic amino acids,
their catabolites, and vegetable-derived compounds were longitudinally associated
with short-term and working memory. Functionally, microbiota transplantation from
human subjects with obesity led to decreased memory scores in mice, aligning this
trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal
cortex of mice revealed that short-term memory associated with aromatic amino acid
pathways, inflammatory genes, and clusters of bacterial species. These results highlight
the potential therapeutic value of targeting the gut microbiota for memory impairment,
specifically in subjects with obesity.