NUTRIENTS ACUTELY MODULATE INTESTINAL PERMEABILITY INDEPENDENTLY OF THE ENTERIC NERVOUS SYSTEM
Authors: Cavin Jean‐Baptiste , MacNaughton Wallace K. , Sharkey Keith A. 
Published: June 2021

BackgroundIt is well known that diet profoundly affects intestinal physiology, with some diets contributing to a “leaky gut”, possibly promoting IBD and metabolic syndrome. Recently, several studies have suggested that the enteric nervous system, composed of neurons and glial cells, could be a potent regulator of intestinal permeability. We hypothesize that nutrients, sensed at the level of the epithelium, could trigger a neuroglial response to regulate intestinal permeability.AimsWe investigated whether nutrients acutely modulate intestinal permeability at the level of the small intestine and if the enteric nervous system plays a role in this effect.MethodsIntact jejunum and Ileum segments from CD1 mice were mounted in Ussing chambers. Transepithelial electrical resistance (TER) and short circuit current (Isc) were recorded for 50 min after stimulation with different nutrients. Two different size probes, 400 Da Fluorescein isothiocyanate (FITC) or 4000 Da FITC‐Dextran (FD4), were used as markers of intestinal permeability. Apical glucose, fructose, glutamine (10 mM) or 5% Intralipid® were used as nutrient stimuli. Enteric neurons were either inhibited with tetrodotoxin (TTX, 0.5 μM) or activated with veratridine (10 μM). Enteric gliotransmission was inhibited with the connexin 43 blocker Gap26 (20 μM).ResultsThe nutrients used in this study were “sensed” by the intestinal epithelium as illustrated by a rapid change in Isc following stimulation (+14, +7, −28 μA/cm2 for glucose, glutamine and Intralipid, respectively, in the jejunum; +132, +42, −14, −56 μA/cm2 for glucose, glutamine, fructose and Intralipid in the ileum). Addition of 5% Intralipid to the luminal side increased TER in both jejunum (+10 Ω/cm2) and Ileum (+10 Ω/cm2). Glutamine triggered a significant (p<0.05) increase of the transport of FITC across the intestine (+600% in jejunum and +60% in ileum after 50 minutes). On the other hand the transport of both FITC and FD4 was significantly reduced in the presence of Intralipid (−73% and −27%, respectively, in the jejunum and −74% and −31%, in the ileum). Results were similar when germ free mice were compared to conventionally raised mice. Neither the activation or inhibition of enteric neurons or the inhibition of gliotransmission affected TER or the transport of the fluorescent probes across the mouse intestine. Additionally, the use of the neuronal blocker, TTX, did not reverse the glutamine‐ or Intralipid‐induced alteration of FITC and FD4 transport across the intestine. Blocking the calcium‐sensing receptor did not alter the response to glutamine.ConclusionsWe have shown glutamine and Intralipid® to be potent regulators of intestinal permeability acting independently of the enteric nervous system, the microbiota, and the calcium‐sensing receptor. We are currently investigating the potential endocrine contribution to these effects.Support or Funding InformationThe work of Dr. Cavin was supported by a postdoctoral fellowship from the Human Frontier Science Program Organization and Alberta innovates.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.