Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis¹. Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract². A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal pathologies with an underlying microbial component^3,4,5,6, but the direct effect of dying mammalian cells on bacterial growth is unclear. Here we advance a concept that several Enterobacteriaceae, including patient-derived clinical isolates, have an efficient growth strategy to exploit soluble factors that are released from dying gut epithelial cells. Mammalian nutrients released after caspase-3/7-dependent apoptosis boosts the growth of multiple Enterobacteriaceae and is observed using primary mouse colonic tissue, mouse and human cell lines, several apoptotic triggers, and in conventional as well as germ-free mice in vivo. The mammalian cell death nutrients induce a core transcriptional response in pathogenic Salmonella, and we identify the pyruvate formate-lyase-encoding pflB gene as a key driver of bacterial colonization in three contexts: a foodborne infection model, a TNF- and A20-dependent cell death model, and a chemotherapy-induced mucositis model. These findings introduce a new layer to the complex host–pathogen interaction, in which death-induced nutrient release acts as a source of fuel for intestinal bacteria, with implications for gut inflammation and cytotoxic chemotherapy treatment.

受调节的细胞死亡是生命不可或缺的一部分，对生物体发育和体内平衡具有广泛影响¹。受调节的细胞死亡过程中的故障，包括死亡细胞的清除，可以在包括胃肠道²在内的各种组织中表现为多种病理。细胞死亡和具有潜在微生物成分的胃肠道病理之间存在一种长期被认可但难以定义的关系^3,4,5,6, 但垂死的哺乳动物细胞对细菌生长的直接影响尚不清楚。在这里，我们提出了一个概念，即包括患者来源的临床分离株在内的几种肠杆菌科具有有效的生长策略，可以利用垂死的肠道上皮细胞释放的可溶性因子。caspase-3/7 依赖性细胞凋亡后释放的哺乳动物营养物质促进了多种肠杆菌科的生长，并使用原代小鼠结肠组织、小鼠和人类细胞系、几种细胞凋亡触发因素以及传统小鼠和无菌小鼠体内进行了观察。哺乳动物细胞死亡营养素在致病性沙门氏菌中诱导核心转录反应，我们确定了丙酮酸甲酸裂解酶编码pflB基因作为三种情况下细菌定植的关键驱动因素：食源性感染模型、TNF 和 A20 依赖性细胞死亡模型以及化疗引起的粘膜炎模型。这些发现为复杂的宿主-病原体相互作用引入了一个新层次，其中死亡诱导的营养释放充当肠道细菌的燃料来源，对肠道炎症和细胞毒性化疗治疗有影响。