Profiling Luminal pH in Three-Dimensional Gastrointestinal Organoids Using Microelectrodes

The overall goal of our research is to understand how gastric epithelial cells, immune cells, stromal cells and their products, such as cytokines and mucus, work together to respond to infection with gastric pathogen helicobacter pylori. To that end, we are trying to build complex physiologically relevant models of the human gastric mucosa. Previous studies with gastric organoids have shown conflicting results regarding the ability of these models to maintain acid-secreting parietal cells.

Using the pH microelectrodes, we demonstrated that in the absence of specific differentiation or stimulation protocols, human gastric organoids maintain a near neutral pH in the lumen. Relative in accessibility, the organoid lumen has long restricted our understanding of the microenvironment within. We demonstrate the first successful microelectrode pH measurements for the functional characterization of organoids.

Our microelectrode-based method could provide researchers with a reliable tool that can be adapted to their specific needs. Until now, pH measurement within gastrointestinal organoids has involved the use of pH-sensitive dyes that rely on microscopic imaging for quantification. The main advantage of using microelectrodes is that they provide accurate numerical pH readings.

In addition, intraluminal pH can be recorded in real time and with superior spatial resolution. We are working toward a fully functional model of the human gastric mucus layer with the physiological pH gradient so we can study the role of this barrier in helicobacter pylori infection. The ultimate goal is to develop new cytoprotective treatments that strengthen the mucus layer and prevent bacterial invasion.