The small intestine contains a two-front nutrient supply environment created by luminal dietary and microbial metabolites (enteral side) and systemic metabolites from the host (serosal side). Yet, it is unknown how each side contributes differentially to the small intestinal physiology. Here, we generated a comprehensive, high-resolution map of the small intestinal two-front nutrient supply environment. Using in vivo tracing of macronutrients and spatial metabolomics, we visualized the spatiotemporal dynamics and cell-type tropism in nutrient absorption and the region-specific metabolic heterogeneity within the villi. Specifically, glutamine from the enteral side fuels goblet cells to support mucus production, and the serosal side loosens the epithelial barrier by calibrating fungal metabolites. Disorganized feeding patterns, akin to the human lifestyle of skipping breakfast, increase the risk of metabolic diseases by inducing epithelial memory of lipid absorption. This study improves our understanding of how the small intestine is spatiotemporally regulated by its unique nutritional environment.

中文翻译：

---

双前营养供应环境通过营养吸收和宿主防御的差异调节为小肠生理提供燃料


小肠包含由管腔饮食和微生物代谢物（肠内侧）和来自宿主的全身代谢物（浆膜侧）创造的双前营养供应环境。然而，目前尚不清楚每一侧如何对小肠生理学做出不同的贡献。在这里，我们生成了小肠双前营养供应环境的全面、高分辨率图谱。 使用宏量营养素的体内示踪和空间代谢组学，我们可视化了营养吸收的时空动力学和细胞类型趋向性以及绒毛内区域特异性代谢异质性。具体来说，来自肠内侧的谷氨酰胺为杯状细胞提供燃料以支持粘液产生，浆膜侧通过校准真菌代谢物来松动上皮屏障。杂乱无章的喂养模式，类似于人类不吃早餐的生活方式，通过诱导脂质吸收的上皮记忆来增加代谢性疾病的风险。这项研究提高了我们对小肠如何受到其独特营养环境的时空调节的理解。