Targeting the gut: Simulating disease models and their treatments in the gastrointestinal tract with in vitro methods

Karl-Herbert Schäfer

Department of Biotechnology, University of Applied Sciences Kaiserslautern, 66482 Zweibrücken, Germany

The gastrointestinal tract is, besides skin and lung, one of the major gates for the delivery of pharmaceutical compounds. But the gut is also involved in many diseases that are not primarily related to the gastrointestinal tract, such as i.e. cancer or stroke. In recent years, there is increasing evidence, that the gut plays also a key role in the etiology of neurodegeneration.

So, the gut is a target organ to treat locally or systemically all kind of diseases, but might likewise be the place to address in search of biomarkers for the early diagnosis of Alzheimers or Parkinsons disease.

In general, the gastrointestinal tract can be affected by any compound which is administered both orally or intravenously. We are using several in vitro approaches to investigate both side effects, as well as therapeutical potencies concerning inflammatory or oxidative stress components.

We are using techniques that focus on the gut innervation, such as primary cultures of the enteric nervous system. These cultures can be stimulated by the compound investigated and changes in neural growth or proliferation can be assesed. Moreover, neuronal networks can be cultivated on so called multi-electrode-arrays (MEA). These MEAs allow to record electrical activities under the influcence of pharmacological agents or pathological stimuli, such as amyloid-beta, and can also be combined with optical readyouts (calcium imaging).

We are are also using techniques that investigate the whole gut. Small intestinal segments can be excised with the adjacent bloodvessels and kept for several hours or days in an organ bath culture. A mesenterial perfusion allows to study the effects of systemic and oral administration. The read-out of that approach can be either the optical or electrical recording of the motilty, but also the analysis of the complete tissue at the end of the experiment. In a current study we are investigating the potential of herbal (herbs, fungi, cyanobacteria) compounds such as Galliellalactone concerning their antioxidative or neuroprotective effect.

In general, in vitro evaluations of both isolated enteric nervous system or whole gut preparations, allows the analysis of primary or side effects of pharmacological compounds, as well as early changes in gut composition or function in diseases.