Dissertation
Gut Microphysiological Systems for Toxicology: Scalable Assays for Industry Implementation
Every day, the intestines face an enormous challenge. They must absorb nutrients, medicines, and other substances we consume, while keeping harmful compounds out.
- Author
- M.L. Morelli
- Date
- 12 May 2026
- Links
- Thesis in Leiden Repository
The thin layer of cells lining the gut wall is central to this balance, and when disrupted, the consequences can range from inflammation to serious illness. Understanding how drugs, food contaminants, and toxic substances affect this lining is therefore a critical task. Yet the laboratory tools currently used, such as dishes of cells or animal experiments, do not always fully capture what happens in the human gut.This thesis developed and tested miniaturized gut models known as "gut on chip" systems. These tiny devices grow human intestinal cells under conditions that mimic the gut's real environment, including fluid flow and a three dimensional tissue structure. Because they more closely resemble the actual human intestine, they have the potential to provide more physiologically relevant predictions than conventional static cell culture models. In this thesis, they were used to study how inflammatory and toxic stimuli affect the gut lining, capturing signs of injury that are difficult to evaluate with conventional laboratory methods.To make this technology practical, the thesis applied established measurement methods, such as electrical signals, microscopic images, and biological markers to assess cell health, alongside structured image analysis pipelines ensuring reproducibility across quantitative readouts.Taken together, this work brings gut on chip technology a step closer to complementing conventional tests and reducing animal experiments, with the potential to support more efficient and patient-relevant drug development pipelines.