(729) Gut Microbiome is Persistently Altered by Maternal Western-Style Diet Exposure Despite Weaning Diet

Gut microbes moderate and/or produce metabolites like serotonin and short-chain fatty acids (SCFAs) that are crucial for normal behavior. In a Japanese macaque model, offspring exposed to maternal Western-Style diet (mWSD) display anxiety, despite being weaned onto a control diet. We hypothesized that maternal mWSD alters the gut microbiome’s ability to moderate the production of serotonin and SCFA pathway metabolites, contributing to the anxiety phenotype.

Study Design:

Dams were fed a Chow control diet or mWSD during pregnancy and lactation, then offspring were weaned onto Chow or Western-Style diet. Voided stool, colon contents, and intestinal mucosa were sampled throughout development ranging from fetal (gestational day 130) to pre-puberty (36-40 months) (Fig. 1A). DNA from these tissues (total n=1223 + n=27 kit negative controls) underwent whole-genome sequencing, taxonomic classification with MetaPhlAn4, functional classification with HUMAnN3, and differential abundance determination by MaAsLin2.

Results:

mWSD drove differential abundance of n=37 taxa in voided stool, independent of offspring sex, offspring diet, or repeat sampling. Presented at the family level, mWSD was associated with depleted Campylobacteraceae (p=0.002) and Lactobacillaceae (p=0.018), and enriched Lachnospiraceae (p=0.034) and Ruminococcaceae (p=0.028) (FDR adjusted p values) (Fig. 1B). At the functional level, mWSD was associated with suppression of gene expression, with n=395 genes down-regulated vs n=122 up-regulated (2-fold change threshold). Genes responsible for tryptophan (serotonin’s precursor) availability and SCFA phosphorylation were persistently downregulated at all time points in stool from offspring of dams fed a mWSD (Fig. 1C).

Conclusion:

Gut microbiome composition and bacterial gene function were found to be significantly altered by mWSD exposure, even when offspring were weaned onto and fed a control diet for 2.5 years. Downregulation of serotonin’s precursor and SCFA-related gene functions may promote the increased anxiety observed in these offspring via altered microbe-to-host signaling in the gut.