Decoding intestinal barrier dynamics: in vitro models to study the microbiota-independent and -dependent effects of non-digestible carbohydrates and human milk oligosaccharides
| PhD ceremony: | Ms X. (Xiaochen) Chen |
| When: | October 10, 2025 |
| Start: | 12:45 |
| Supervisors: | P. (Paul) de Vos, prof. dr. M.T.C. (Marthe) Walvoort |
| Where: | Academy building RUG / Student Information & Administration |
| Faculty: | Medical Sciences / UMCG |
Decoding intestinal barrier dynamics
The intestinal barrier is essential for maintaining gut homeostasis by regulating nutrient absorption and preventing the entry of harmful substances. Non-digestible carbohydrates (NDCs) and human milk oligosaccharides (hMOs) have emerged as important modulators of barrier function, acting either directly on epithelial cells or indirectly through microbial fermentation. However, their effects are still not fully understood.
This thesis of Xiaochen Chen developed and applied advanced in vitro models to capture the complex interactions between these oligosaccharides, the microbiota, and the intestinal epithelium. A neuro-epithelial co-culture system combining intestinal epithelial cells with nerve cells was established to study microbiota-independent mechanisms. This model demonstrated that nerve cells protected epithelial integrity and that hMOs could either substitute for or enhance this effect, depending on the type of barrier disruptor.
Additionally, an innovative microbe-host interaction model was created using alginate capsules loaded with infant or adult gut microbiota. This system enabled dynamic fermentation of NDCs or hMOs while continuously monitoring barrier function in real time with the Electric Cell-Substrate Impedance Sensing (ECIS) system. The results revealed age-dependent metabolic profiles: adult microbiota produced more butyrate, resulting in superior intestinal barrier protection compared to infant microbiota. To sum up, these models provide new insights into how the structures of NDCs or hMOs, along with microbial composition, influence intestinal barrier function.
These findings support the use of these in vitro models as valuable tools for guiding the design of targeted dietary interventions to support gut health across different life stages.