Studying neuro-immune-microbiome crosstalk in the gut using the optogenetic organ gut culture system

Abstract

The gastrointestinal tract is densely populated by microorganisms including, bacteria, fungi, viruses, protozoa and archaea, collectively known as the gut microbiome. Previous research has established the critical role the gut microbiome has in an individual’s overall health including assisting in digestion, synthesizing nutrients and developing the immune system. In addition to the microbiome, the gut also contains many immune cells and neurons of the enteric nervous system, a subset of the autonomic nervous system that controls peristalsis. To maintain homeostasis, the enteric nervous system, microbiome and immune system need to remain in perfect balance. Changes in this equilibrium are associated with inflammatory bowel disease, cancer and pathologies of the central nervous system (CNS). Understanding this crosstalk has begun to emerge as a valuable approach to the development of therapies to aid in these diseases. Dr. Nissan Yissachar’s novel gut organ culture system has advanced research in this sector by creating a device that facilitates the studying of an entire colon without causing damage and is easier to manipulate than an in vivo model. The research described herein, in which I participated during my summer 2022 internship at Bar-Ilan University, involved a modified version of the original system, that specifically targets the neurons in the gut to activate them and monitor the changes to the crosstalk. Using the system of optogenetics which takes advantage of light as a tool for activating neurons, this system was established as a credible method to study the unique role of the neurons in the gut. Through qPCR, it was found that neuronal activation was associated with immune response. More recently, bacterial therapies are being introduced as a potential aid in decreasing inflammation. Research is still ongoing, but this innovative approach to study neurons in the gut is paving the way for continued research on the crosstalk and its role in disease. This approach can advance the development of modern therapies for many of the gastrointestinal tract.