The small intestine performs multiple critical functions, including nutrient absorption and hormone secretion. It also hosts a diverse community of microorganisms known as the commensal microbiota, which enhances the body’s defense mechanisms. These functions exhibit spatiotemporal heterogeneity and specialization, varying across time and location. Through these specialized roles, the small intestine influences both local and systemic physiology.
To fulfill these functions, the small intestine relies on energy derived from an organized nutrient supply system. It operates within a dual nutrient supply framework: the enteral side (from the intestinal lumen) and the serosal side (from the outermost layer of the intestine). While the enteral side receives metabolites from dietary and microbial sources, the serosal side obtains nutrients from the host’s systemic circulation.
Zhang et al. investigated how the unique nutritional environment regulates the small intestine’s spatiotemporal functions. They demonstrated that each nutrient supply route has distinct physiological effects. For instance, intravenous and intraduedonal glucose produce different appetite responses in humans. This findings highlights how the route of nutrient entry significantly influences systemic responses and risk of metabolic disorders. The researchers mapped the small intestine’s dual nutrient supply system and visualized region-specific metabolic heterogeneity within the villi. They also explored how disruptions in these nutrient supply modes could lead to disease.
The study employed three mouse feeding models, each using different nutrient supply sources. All groups initially received a standard diet with tail vein saline infusions. Before tissue collection, the sham group was fed orally, simulating a normal feeding state. The TPN (total parenteral nutrition) group received only tail-vein-infused TPN, while the starvation group received no nutrients.
Gut interstitial fluid (GIF) was extracted to represent the internal environment of the small intestinal tissue. The GIF includes inputs from both the enteral and serosal sides, along with protein factors. Cross-scale analyses, including metabolomics and proteomics, were performed to investigate biological processes. To evaluate the effects of the enteral supply, comparisons were made between the sham and TPN groups, while the TPN and starvation groups highlighted the serosal supply’s role.
The analyses revealed that lipid-related metabolites were primarily associated with the enteral side, whereas carbohydrate and organic acid metabolites were linked to the serosal side. Microbial-derived metabolites constituted a significant portion of the GIF, underscoring the microbiota’s crucial role in intestinal health. Dietary interventions shape the microbiota and impact intestinal homeostasis. For instance, skipping breakfast alters the balance of microbial metabolites, affecting mucus production and intestinal defense. Glutamine from the enteral side facilitates mucus production, ensuring the colonization of commensal bacteria while protecting the intestine from pathogens.
In conclusion, the small intestine operates under precise spatiotemporal regulation by its dual nutrient supply system. These mechanisms contribute to epithelial renewal, mucus production, barrier synchronization, and more. While specific metabolites have been shown to significantly influence intestinal physiology and microbiota, further research is needed to determine whether other metabolites exert similar effects.
Author: Zeynep Ebrar Yolcu
Editor: Fatma Duran
Reference: Jian Zhang,1,2,9 Ruonan Tian,3,9 Jia Liu,4,9 Jie Yuan,4,9 Siwen Zhang,5 Zhexu Chi,1 Weiwei Yu,1 Qianzhou Yu,1 Zhen Wang,1 Sheng Chen,1 Mobai Li,1 Dehang Yang,1 Tianyi Hu,1 Qiqi Deng,1 Xiaoyang Lu,1 Yidong Yang,1 Rongbin Zhou,6 Xue Zhang,7 Wanlu Liu,3,8,* and Di Wang1,2,10,*A two-front nutrient supply environment fuels small intestinal physiology through differential regulation of nutrient absorption and host defense https://doi.org/10.1016/j.cell.2024.08.012
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