The enduring effects of early-life HFHS exposure on feeding behavior 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 high-fat/high-sugar (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 HFHS diet on feeding behavior in adult male and female mice. We show here that an early-life HFHS diet had distinct and time dependent changes on microbiota composition, feeding behavior, and on the expression of key hypothalamic genes involved in energy balance and feeding. Targeting with microbiota-based interventions was sufficient to reverse these enduring effects in adulthood in a sex-dependent manner.

生命早期不健康饮食会影响进食行为的发育与肠道菌群（gut microbiota）的成熟，反之肠道菌群也与食欲及进食行为密切相关。然而，目前针对生命早期高脂肪/高糖（high-fat/high-sugar, HFHS）饮食对成年后进食行为的长期影响的相关研究尚未得到充分阐释。尽管已有研究表明微生物组参与饮食-代谢物互作过程，但其在介导此类持久影响中的具体作用，以及相关治疗干预的潜在可行性仍尚不明确。为此，本研究探讨了靶向肠道菌群的干预手段——包括益生元组合（低聚果糖（fructo-oligosaccharides）与低聚半乳糖（galacto-oligosaccharides），即FOS+GOS），以及候选益生菌长双歧杆菌APC1472（B. longum APC1472）——是否能够逆转生命早期HFHS饮食对成年雌雄小鼠进食行为造成的不良影响。本研究结果显示，生命早期HFHS饮食会对肠道菌群组成、进食行为，以及参与能量平衡与进食调控的关键下丘脑基因的表达产生显著且具有时间依赖性的改变。采用基于肠道菌群的干预手段，足以在成年阶段以性别依赖的方式逆转上述持久影响。