2. Academic Validation
  3. A two-front nutrient supply environment fuels small intestinal physiology through differential regulation of nutrient absorption and host defense

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

  • Cell. 2024 Oct 31;187(22):6251-6271.e20. doi: 10.1016/j.cell.2024.08.012.
Jian Zhang 1,  Ruonan Tian 2,  Jia Liu 3,  Jie Yuan 3,  Siwen Zhang 4,  Zhexu Chi 5,  Weiwei Yu 5,  Qianzhou Yu 5,  Zhen Wang 5,  Sheng Chen 5,  Mobai Li 5,  Dehang Yang 5,  Tianyi Hu 5,  Qiqi Deng 5,  Xiaoyang Lu 5,  Yidong Yang 5,  Rongbin Zhou 6,  Xue Zhang 7,  Wanlu Liu 8,  Di Wang 9
Affiliations

Affiliations

  • 1 Institute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311113, China.
  • 2 Department of Rheumatology and Immunology of the Second Affiliated Hospital, and Centre of Biomedical Systems and Informatics of Zhejiang University, University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China.
  • 3 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 4 Department of Endocrinology & Metabolism, The First Hospital of Jilin University, Changchun 130061, China.
  • 5 Institute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 6 Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, University of Science and Technology of China, Hefei 230027, China.
  • 7 Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 8 Department of Rheumatology and Immunology of the Second Affiliated Hospital, and Centre of Biomedical Systems and Informatics of Zhejiang University, University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, China; Biomedical Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9YL, UK. Electronic address: wanluliu@intl.zju.edu.cn.
  • 9 Institute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311113, China. Electronic address: diwang@zju.edu.cn.
PMID: 39427662 DOI: 10.1016/j.cell.2024.08.012
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.

Keywords

adaptation; breakfast skipping; in vivo metabolite tracing; metabolic heterogeneity; multi-omics; the small intestine; two-front nutrient supply; zonated function of enterocyte.

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