New research from Zhejiang University, published in Cell on Oct 19, reveals critical insights into the dual-source nutrient supply mechanism of the small intestine and its impact on overall health.

The study, led by Professor Wang Di from Zhejiang University School of Medicine and Researcher Liu Wanlu from the Zhejiang University-University of Edinburgh Institute, explores how the small intestine's two distinct nutrient pathways —the dietary ("enteral") and systemic ("vascular") — support intestinal function and influence systemic health.

The researchers discovered that nutrients from food, processed by the intestine itself, largely consist of lipids and bile acids, supporting the gut microbiome. Meanwhile, nutrients delivered through the bloodstream, typically carbohydrates and organic acids, support cell DNA synthesis and immune functions.

Using spatial metabolomics, the team observed that nutrients obtained through eating display specific absorption patterns across different intestinal cell types. For instance, fats are absorbed primarily at the villi tips, while glutamine — an amino acid crucial for maintaining the intestinal mucus barrier — accumulates specifically in goblet cells, which secrete mucus to defend against microbial invasion.

The findings also suggest that intravenous feeding (parenteral nutrition), often used in patients unable to eat, can lead to disruptions in gut health. Without enteral nutrients, the intestines showed increased levels of specific fungi and their metabolite, cytochalasin, which disrupts the gut barrier by loosening cell junctions.

Treatment with antifungal agents helped mitigate these adverse effects, providing potential strategies for managing gut-related complications in patients on long-term parenteral nutrition.

Further experiments showed that skipping breakfast could lead to excessive cholesterol absorption in the intestine, heightening cardiovascular risk by contributing to atherosclerosis.

This study highlights the importance of consistent eating patterns in maintaining gut and metabolic health, offering new clinical perspectives and intervention targets for managing diet-related metabolic disorders.