Crosstalk between omega-6 oxylipins and the enteric nervous system: Implications for gut disorders?

Abstract

The enteric nervous system (ENS) continues to dazzle scientists with its ability to integrate signals, from the outside as well as from the host, to accurately regulate digestive functions. Composed of neurons and enteric glial cells, the ENS interplays with numerous neighboring cells through the reception and/or the production of several types of mediators. In particular, ENS can produce and release n-6 oxylipins. These lipid mediators, derived from arachidonic acid, play a major role in inflammatory and allergic processes, but can also regulate immune and nervous system functions. As such, the study of these n-6 oxylipins on the digestive functions, their cross talk with the ENS and their implication in pathophysiological processes is in full expansion and will be discussed in this review.

Keywords: diet; enteric nervous system; inflammation; omega-3; omega-6.

Figure 1

n-6 Oxylipins derived from arachidonic acid. The metabolism of PUFAs is a complex process involving several enzymes of desaturation, elongation, and β-oxidation. n-6 oxylipins are synthesized from arachidonic acid (ARA) through three major pathways, the first depending on cyclooxygenase (grey), the second on lipoxygenase (yellow), and the third on cytochrome P450 (CYP) monooxygenase activities (green). COX, cyclooxygenase; LOX, lipoxygenase; CYP, cytochrome P450; PGFS, prostaglandin F synthase; PGDS, prostaglandin D synthase, PGES, prostaglandin E synthase; PTGIS, prostaglandin I synthase; TXAS, thromboxane A2 synthase.

Figure 2

n-6 Oxylipins regulate the Enteric nervous system. COX-(grey) or LOX-(yellow) derived n-6 oxylipins increase (↑) different enteric neuron properties (blue) but their impacts on EGCs remain to be determined (?).

Figure 3

Enteric neurons and glial cells produce n-6 oxylipins to regulate the neighboring cells. Some n-6 oxylipin are to regulate glia or neurons, but also to control functions of smooth muscle or intestinal epithelial cells. COX-(grey) or LOX-(yellow) derived n-6 oxylipins produced by enteric neurons and/or glial cells can regulate different enteric neuron properties (blue), but also intestinal epithelial barrier properties (brown) or smooth muscle contraction (black). Marked with a () are cells, oxylipins or cellular functions deficient in chronic inflammatory disease that is Crohn’s disease (CD).