Enteric neuromodulation for the gut and beyond

The small intestine is the longest organ in the human body, spanning a length of ~5 m and compartmentalized into three distinct regions with specific roles in maintenance of comprehensive homeostasis. Along its length exists as a unique and independent system—called the enteric nervous system (ENS)—which coordinates the multitude of functions continuously around the clock. Yet, with so many vital roles played, the functions, relationships, and roles of the small intestine and ENS remain largely elusive. This fundamental hole in the physiology of the small intestine and ENS introduces a substantial number of challenges when attempting to create bioelectronic approaches for treatment of various disorders originating in the small intestine. Here, we review existing therapeutic options for modulating the small intestine, discuss fundamental gaps that must be addressed, and highlight novel methods and approaches to consider for development of bioelectronic approaches aiming to modulate the small intestine.