Use of Human In Vitro Gut Specimens for Translational Neurogastroenterology and Motility in the 21st Century.

There is a huge gap in our understanding of the human ENS and translating data from mice to humans that is important when developing targeted therapeutics. The ENS or "human little brain in the gut" is easily accessible for study in GI surgical or biopsy samples. This mini review is focused on the use of human gut specimens in translating laboratory data on ENS and enteric neuropathies in neurogastroenterology and motility from mice to humans. Availability of viable human gut samples, in combination with technological advances in innovative recording techniques and new in vitro models provide powerful ways to study neural activity and secretomotor function or monitor motility in health and disease with exquisite sophistication and precision. Electrophysiological recordings, optical recordings with voltage-sensitive dyes, or Ca²⁺ imaging (in adult or fetal gut) is used to study neural activity in human ENS in health and disease. 'First in man patch clamp recordings' is possible in isolated networks of human myenteric ganglia, opening the door for patch-seq. The human ENS at single cell resolution (snRNA-seq) revealed cell-diversity, similarities and differences between human and mouse in vitro. Visceral afferent recordings are used for mechanosensation and pain signaling in humans. Stem cell therapies may hold future promise for patients with enteric neuropathies. A greater focus on the human ENS and enteric neuropathies (i.e. IBS, FD, postoperative ileus, CIPO, chronic constipation, Hirschsprung Disease, infection, gastroparesis, Parkinson's disease, IBD, visceral pain) is one important step for consideration in developing potential therapeutics before proceeding to more expensive and complex clinical trials in patients to treat GI Disorders and Diseases.