The Gut-Immune Axis—A Bioelectronic Approach for Studying IBS, Diet and Intestinal Inflammation

Irritable bowel syndrome (IBS) is a chronic bowel disorder associated with abdominal pain and altered bowel movements, broadly classified as diarrhea- or constipation-predominant or mixed. Altered intestinal permeability and immune function have been linked to subsets of IBS(<i>1</i>). Intestinal immune cells play a pivotal role in regulating intestinal homeostasis and are key role players in inflammatory responses and maintenance of barrier integrity(<i>2</i>). Understanding the intricate interplay between the intestinal epithelium and immune cells is therefore important in broadening our understanding of IBS as well as intestinal inflammation and its modulation by diet. Traditional <i>in vitro</i> intestinal models often focus on the epithelial layer to study barrier function and transport processes, however it is becoming increasingly recognized that incorporation of immune cells in these models is crucial for improving our understanding of inflammation and immune responses(<i>3</i>).<br/><br/><b>Methods</b><br/><br/>We introduce a novel <i>in vitro</i> model of the gut-immune and gut-immune-vasculature interface, offering a more physiologically-relevant platform to investigate the effects of IBS and the dynamics of intestinal inflammation. The model integrates key components of the gut microenvironment, including epithelial and immune cells, contained within a collagen-based hydrogel, with or without vascular endothelial cells. We use this model to explore the effects of hallmarks of healthy (short chain fatty acids) and western (long chain fatty acids) diets as well as faecal supernatants from patients suffering from IBS, pre- and post-dietary intervention, and their healthy household controls. To do this we focus on monitoring changes in intestinal barrier integrity using both a conventional transepithelial electrical resistance (TEER) monitoring approach relying on chop-stick electrodes and a novel Parylene C and PEDOT:PSS based conformable device(<i>4</i>).<br/><br/><b>Results & Discussion</b><br/><br/>Our findings demonstrate that barrier integrity changes in response to both pro-inflammatory and anti-inflammatory stimuli can be measured electrically. Additionally, we show that TEER changes induced by incubation with faecal supernatants from IBS patients can be effectively measured, including changes post dietary intervention. Our results indicate that our conformable devices are more sensitive and capable of detecting these changes compared to conventional methods.<br/><br/><b>Conclusion</b><br/><br/>The study confirms that dietary metabolites and IBS faecal supernatants impact the gut-immune and gut-immune-vasculature interfaces, and that these effects can be effectively monitored using novel conformable devices. This provides a valuable platform and monitoring technique for IBS and metabolic research, allowing for detailed study of the effects of diet and disease states on intestinal barrier integrity.<br/><br/><b>References </b><br/><br/>1. N. Hanning <i>et al.</i>, <i>Ther. Adv. Gastroenterol.</i> <b>14</b>, 175628482199358 (2021).<br/>2. T. E. Adolph <i>et al.</i>, <i>Nat. Rev. Gastroenterol. Hepatol.</i> <b>19</b>, 753–767 (2022).<br/>3. A. E. Wheeler, V. Stoeger, R. M. Owens, <i>Lab. Chip</i>. <b>24</b>, 1266–1292 (2024).<br/>4. S. L. Barron <i>et al.</i>, <i>Adv. Mater.</i> <b>36</b>, 2306679 (2024).