In vivo gut-brain optogenetic endomicroscopy for digestive disorders management

Proper functioning of the digestive system depends largely on the enteric nervous system (the gut’s brain), which on one side is linked to the gut’s microbiota and on the other side is linked to environmental factors, like stress, via gut-brain axis.

Communication along this axis is not very well understood, even though it is crucial for the diagnosis and treatment of functional digestive disorders, which are the most common problems in the digestive system imposing a significant burden on public health.

One of the limiting factors is the lack of tools enabling investigation of gut’s neuronal network in vivo.The goal of this proposal is to provide an insight into the functioning of microbiota-gut-brain axis in vivo.

We will develop a novel optogenetic endomicroscope based on Optical Coherence Tomography (OCT) capable of mapping the morphology and the functionality of the enteric nervous system and microbiota sampling.

We hypothesize that such tool, in addition to direct analysis of the gut status in various digestive conditions, can also be indirectly used to stimulate the brain response via gut-brain axis.

To test our hypothesis, we will co-register performance of the proposed method with functional magnetic resonance imaging to investigate in animal models 1) the response of the brain to activation of serotonin neurons in the gut and 2) the response of the gut to optogenetically induced depression at the brain level.

Any tool improving understanding of interactions between microbiota, gut and brain would be of paramount importance for improving management of many patients with digestive disorders.

Moreover, such information has potential to introduce novel diagnosis and treatment paradigm in obesity, and other diseases like Parkinson disease or Alzheimer disease.

With the ultimate goal of transferring our finding into humans, we will be focused on finding OCT-specific designs and biomarkers for diagnosing diseases linked to dysfunction of this axis.