NUTRIENTS ACUTELY MODULATE INTESTINAL PERMEABILITY INDEPENDENTLY OF THE ENTERIC NERVOUS SYSTEM
Notice bibliographique
Résumé
Background It 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. Aims We 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. Methods Intact 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). Results The 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. Conclusions We 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 Information The 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 .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».