Infection-induced aversion against enteropathogens is a conserved sickness behaviour that can promote host survival^1,2. The aetiology of this behaviour remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviours against toxic microorganisms^3,4,5. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviours remains unknown. Here we show that enteropathogen infection in Drosophila can modulate olfaction through metabolic reprogramming of ensheathing glia of the antennal lobe. Infection-induced unpaired cytokine expression in the intestine activates JAK–STAT signalling in ensheathing glia, inducing the expression of glial monocarboxylate transporters and the apolipoprotein glial lazarillo (GLaz), and affecting metabolic coupling of glia and neurons at the antennal lobe. This modulates olfactory discrimination, promotes the avoidance of bacteria-laced food and increases fly survival. Although transient in young flies, gut-induced metabolic reprogramming of ensheathing glia becomes constitutive in old flies owing to age-related intestinal inflammation, which contributes to an age-related decline in olfactory discrimination. Our findings identify adaptive glial metabolic reprogramming by gut-derived cytokines as a mechanism that causes lasting changes in a sensory system in ageing flies.

感染引起的对肠道病原体的厌恶是一种保守的疾病行为，可以促进宿主存活^1,2。这种行为的病因仍然知之甚少，但对果蝇的研究已将嗅觉和味觉知觉与对有毒微生物的回避行为联系起来^3,4,5。肠道感染是否以及如何直接影响感官知觉以诱导或调节此类行为仍然未知。在这里，我们展示了果蝇中的肠病原体感染可以通过触角叶鞘胶质细胞的代谢重编程来调节嗅觉。肠道中感染诱导的未配对细胞因子表达激活鞘神经胶质中的 JAK-STAT 信号，诱导神经胶质单羧酸转运蛋白和载脂蛋白神经胶质 lazarillo ( GLaz), 并影响触角叶胶质细胞和神经元的代谢耦合。这会调节嗅觉辨别力，促进避免含有细菌的食物并增加苍蝇的存活率。虽然在年轻果蝇中是短暂的，但由于与年龄相关的肠道炎症，肠道诱导的鞘神经胶质细胞代谢重编程在老年果蝇中成为组成性的，这导致嗅觉辨别能力与年龄相关的下降。我们的研究结果将肠道衍生细胞因子进行的适应性神经胶质代谢重编程确定为导致衰老果蝇感觉系统持久变化的机制。