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44: Maternal diet persistently alters the developing juvenile microbiome in a primate model of obesity

      Objective

      Dysbiosis of the microbiome has been previously associated with obesity. Additionally, it has been hypothesized that obesity begets obesity, and our lab has demonstrated that a high fat (HF) maternal diet can alter the fetal epigenome. Therefore, we aimed to determine if, when, and how maternal diet influences the developing fetal microbiome.

      Study Design

      Japanese macaque dams (n=26) were fed either a control (13%) or high-fat (35%) diet. Offspring were born vaginally and maintained on a maternal diet until weaning. At weaning (4-6 months of age) offspring were either maintained on the maternal diet (control vs HF) or were switched to the opposing diet (crossover cohort, HF vs control). At one year of age, the microbiome of the juvenile’s stool, anus, or colon was examined via deep sequencing (16S V3V5 rRNA; 454FLXTitanium). Data was QC filtered and analyzed using QIIME. Differential Campylobacter abundance was confirmed by bacterial genus and species specific qPCR.

      Results

      Juveniles exposed to a HF diet in utero clustered distinct from those of control diet fed dams. Further, this clustering was maintained when juveniles exposed to a HF diet were switched to a control diet post-weaning (Permanova, p=0.016; panel A). Specifically, upon exposure to a HF diet (be it in utero or post-weaning), Campylobacter was no longer detected in the gut of the offspring (panel B). Switching to a control diet post weaning (crossover cohorts) did not rescue this affect, and was confirmed by targeted analysis (panel C).

      Conclusion

      These data suggest that a high fat maternal diet persistently alters the juvenile microbiome out to one year of age. Collectively, our prior findings and these new results make evident that maternal influences occur irrespective of maternal habitus and are seen in dams that are sensitive (obese) or resistant (lean) to a high-fat diet. We speculate that alterations in the maternal diet may propagate their affects long-term through alterations in the offspring microbiome.
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