The enduring effects of early-life HFHS exposure on feeding behavior and hypothalamic transcriptome are sensitive to Bifidobacterium

An unhealthy diet in early-life impacts on the development of eating behavior and the gut microbiota, and conversely the microbiota is implicated in appetite and eating behavior. However, the enduring effects of early-life HFHS on later life feeding behavior are less well described. Although the microbiome has been implicated in diet-metabolite interactions, its role in the enduring effects and potential for therapeutic intervention are unclear. To this end, we investigated whether microbiota-targeted interventions (a prebiotic combination (fructo-oligosaccharides and galacto-oligosaccharides), FOS+GOS) or a putative probiotic (B. longum APC1472)) could restore any adverse effects of early-life high-fat/high-sugar (HFHS) diet on feeding behavior in adult male and female mice. Early-life HFHS diet had distinct and time dependent changes on feeding behavior, microbiota composition, and hypothalamic genes involved in energy balance and response to peptidoglycan in adult female and male mice, with greater enduring effects in females. Targeting with microbiota-based interventions was sufficient to reverse these enduring effects in adulthood in a sex-dependent manner.