Optogenetic control of the enteric nervous system and gastrointestinal transit

Introduction: There are limited effective therapies available for improving gastrointestinal (GI) transit in mammals with intractable or chronic constipation. Current therapeutics to improve GI-transit usually require oral ingestion of therapeutic drugs, such as the serotonin receptor agonist prucalopride. However, most receptors are distributed all over the body and unsurprisingly drugs like prucalopride stimulate multiple organs, often leading to unwanted side effects. There is a desperate need in the community to improve GI-transit selectively without effects on other organs. Areas covered: We performed a systematic review of the literature on Pubmed and report significant technical advances in optogenetic control of the GI-tract. We discuss recent demonstrations that optogenetics can be used to potently control the activity of subsets of enteric neurons. Special focus is made of the first recent demonstration that wireless optogenetics can be used to stimulate the colon in conscious, freely-moving, untethered mice causing a significant increase in fecal pellet output. This is a significant technical breakthrough with a major therapeutic potential application to improve GI-transit. Expert opinion: The ability to selectively stimulate the ENS to modulate GI-transit in live mammals using light, avoids the need for oral consumption of any drugs and side effects; by stimulating only the GI-tract.