A two-front nutrient supply environment fuels small intestinal physiology through differential regulation of nutrient absorption and host defense

IF 5.7 1区化学 Q2 CHEMISTRY, PHYSICAL Journal of Chemical Theory and Computation Pub Date : 2024-10-19 DOI:10.1016/j.cell.2024.08.012

Jian Zhang, Ruonan Tian, Jia Liu, Jie Yuan, Siwen Zhang, Zhexu Chi, Weiwei Yu, Qianzhou Yu, Zhen Wang, Sheng Chen, Mobai Li, Dehang Yang, Tianyi Hu, Qiqi Deng, Xiaoyang Lu, Yidong Yang, Rongbin Zhou, Xue Zhang, Wanlu Liu, Di Wang

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Abstract

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.

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双线营养供应环境通过对营养吸收和宿主防御的不同调控促进小肠生理机能的发展

小肠包含一个由管腔饮食和微生物代谢物（肠道侧）以及来自宿主的全身代谢物（血清侧）共同创造的双向营养供应环境。然而，目前还不清楚两侧如何对小肠生理产生不同的影响。在这里，我们绘制了一张全面、高分辨率的小肠两侧营养供应环境图。利用体内宏量营养素追踪和空间代谢组学，我们可视化了营养吸收的时空动态和细胞类型倾向性，以及绒毛内特定区域的代谢异质性。具体来说，来自肠道一侧的谷氨酰胺可促进鹅口疮细胞分泌粘液，而来自浆膜一侧的谷氨酰胺则可通过校准真菌代谢物来松弛上皮屏障。无序的进食模式类似于人类不吃早餐的生活方式，会通过诱导上皮对脂质吸收的记忆而增加患代谢性疾病的风险。这项研究加深了我们对小肠如何通过其独特的营养环境进行时空调节的理解。

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来源期刊

Journal of Chemical Theory and Computation 化学-物理：原子、分子和化学物理

CiteScore

9.90

自引率

16.40%

发文量

568

审稿时长

1 months

期刊介绍： The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.