29: Exposure to a high fat diet is associated with persistent alterations in behavior and the gut microbiome in juvenile offspring primates

Abstract

Prior work from our consortium shows that maternal high-fat diet (HFD) consumption is associated with modifications in behavior and the central serotonergic system in juveniles at 1 year of age. Additionally, we have described dysbiosis of the gut microbiome occurring at this age with exposure to maternal HFD. Intriguingly, ∼90% of serotonin (5HT) is made in the gut, and microbes and their metabolites function as important regulators of 5HT production. Here, we aimed to determine the importance of exposure to a HFD as a persistent behavioral mediator in juvenile offspring by examining the associations between diet, behavior, and the gut microbiome. Using our Japanese macaque model of maternal HFD exposure, we performed 16S or whole genome shotgun (WGS) sequencing on stool samples (n=15) collected at 1 & 3 years of age. WGS was performed on the Illumina HiSeq platform and resultant sequences were trimmed/quality filtered using KneadData. Taxonomic classification and functional annotation of species-specific (MetaPhlAn2) and community level metabolic pathways (HUMAnN2) was performed. Stool 5HT levels were assayed by ELISA. Behavioral testing (i.e. novel objects, repetitive behavior) occurred to associate with 5HT and microbiome data. Exposure to HFD in gestation is associated with persistent behavioral modifications (increased anxiety) in offspring at 3 years of age (Fig A). Additionally, we found alterations in metabolic pathways by metagenomic analysis (0.9 billion reads, average 62 million reads/sample) that have been previously shown to modulate 5HT; this includes L-tryptophan biosynthesis, of which Phascolarctobacterium succinatutens was identified as a primary contributor (Fig B). Furthermore, we detected significant inverse correlations with specific taxa, including Phascolarctobacterium and 5HT at 3 years of age (Fig C). Altogether, our data suggest HFD exposure leads to persistent gut microbial dysbiosis associated with reductions in serotonergic signaling mediators and 5HT synthesis that are detectable at 3 years. The interplay between the gut microbiome and serotonergic signaling potentially contribute to behavioral modifications observed with HFD exposure during fetal life, even with consumption of a postnatal control diet.