23: The fetal microbiome is altered in association with maternal diet during gestation

Abstract

Adverse in utero conditions and dysbiosis of the gut microbiome are associated with metabolic disease. Prior studies demonstrate that the gut microbiome is largely influenced by diet, and our previous study shows that maternal diet is associated with persistent dysbiosis of the offspring microbiome at one year of age. Here, we aim to determine if dysbiosis associated with maternal diet exposure can occur in utero and can be ameliorated through interventions in our non-human primate model. Japanese macaque dams were fed a control (CTR) or high-fat diet (HFD). Additionally, therapeutic interventions using resveratrol (RESV) and diet reversal (REV) were utilized during pregnancy. Dams were socially housed and at gestational day 130 (G130), offspring were delivered by Cesarean, and swabs of the fetal colon and oral cavity were obtained, as well as maternal oral, anal, and vaginal samples (42 samples in total). In a second cohort of animals, offspring were vaginally delivered at term (167 days) and maintained on the maternal diet through weaning (n=21). 16S sequencing for microbial DNA was performed. We found that the fetal microbiome is significantly altered by maternal CTR versus HFD (p=0.035, Fig A), and Pasteurellaeis is significantly increased with exposure to a maternal HFD (p<0.05, Fig B). Additionally, we found that the offspring gut microbiome is altered by maternal dietary exposures at 6 and 10 months of age (Fig A). In agreement with our prior studies, we found that Campylobacter was absent when offspring were ever exposed to a HFD (p<0.05, Fig B). The microbial metagenomic pathways mirrored and extended these findings, with changes in HFD-driven microbial bile secretion during gestation, tryptophan metabolism during nursing, and butanoate metabolism post-weaning (p<0.05, Fig C). Altogether, our data demonstrate that a maternal HFD impacts the developing microbiome in utero (fetal data) and these influences have a persistent influence on offspring (6 & 10 months of age). Furthermore, our microbial metabolic pathway data suggest that the footprint of the maternal HFD has both age-specific and long-lasting impacts on the gut microbiome community structure and metabolic function. These pathways may provide novel opportunities to prevent dysbiosis of the microbiome and adult metabolic disease.