• enteric nervous system
• brain/gut interaction
• neurogastroenterology

The GI tract faces a great challenge as it needs to organise nutrient uptake while at the same time prevent toxic substances and harmful organisms from entering the host. To execute this complex task, the intestinal wall is endowed with a myriad of cell types (muscle, neurons, glia, interstitial cells, endocrine, immune and epithelial cells, and vasculature) that have to work in concert. These cells are meticulously organised in concentric layers, within which the enteric nervous system (ENS) controls gut motility, blood flow and secretion.1 Scattered throughout these layers, especially in the lamina propria, are different immune cells that constitute the prime line of defence.

The ENS consists of glia and different populations of neurons that communicate like any other nervous system via synaptic contacts. The enteric presynaptic terminals contain mitochondria and a host of presynaptic proteins necessary for synaptic neurotransmitter release. As part of their synaptic machinery, these terminals also contain α-synuclein. Like anywhere else in the body, ENS α-synuclein can get misfolded and give rise to Lewy body and Lewy neurite type of pathology. Since patients with Parkinson’s disease (PD) often present with GI problems (eg, constipation and dysphagia) likely caused by a dysfunctional ENS, the idea rose that the gut may be involved, even in the initiation of PD. Based on postmortem assessments of the stomach, brainstem and midbrain tissue, Braak et al expanded his staging hypothesis to include the intestine as possibly one of the earliest compartments affected.2

A vast amount of literature, older and recent,3 4 is now available, proving …