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Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway

Intestinal peristalsis is vital for gastrointestinal physiology and host homeostasis and is frequently dysregulated in intestinal disorders. Gut microbiota can regulate gut motility, especially through the tryptophan metabolism pathway. However, the role of indoles as microbial tryptophan metabolite...

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Autores principales: Chen, Ying, Pan, Ruili, Mei, Liya, Tian, Peijun, Wang, Linlin, Zhao, Jianxin, Chen, Wei, Wang, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574622/
https://www.ncbi.nlm.nih.gov/pubmed/37836566
http://dx.doi.org/10.3390/nu15194282
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author Chen, Ying
Pan, Ruili
Mei, Liya
Tian, Peijun
Wang, Linlin
Zhao, Jianxin
Chen, Wei
Wang, Gang
author_facet Chen, Ying
Pan, Ruili
Mei, Liya
Tian, Peijun
Wang, Linlin
Zhao, Jianxin
Chen, Wei
Wang, Gang
author_sort Chen, Ying
collection PubMed
description Intestinal peristalsis is vital for gastrointestinal physiology and host homeostasis and is frequently dysregulated in intestinal disorders. Gut microbiota can regulate gut motility, especially through the tryptophan metabolism pathway. However, the role of indoles as microbial tryptophan metabolites in colonic function requires further exploration. Here, we show that the delivery of indole acetic acid (IAA) targeting the colon can improve gut motility by activating the aryl hydrocarbon receptor (AHR). To achieve colon-targeted delivery, Eudragit S-100 (ES) and chitosan (CS) were used as drug carriers. After optimisation, IAA-loaded ES-coated CS nanoparticles exhibited an encapsulation efficiency of 83% and a drug-loading capacity of 16%. These nanoparticles exhibited pH-dependent characteristics and remained stable in acidic conditions and the upper intestine. In simulated intestinal fluid (pH 7.4) and colonic lumen, considerable amounts of IAA were released after approximately 4 h. Compared with free IAA, the nanoparticles exerted enhanced therapeutic effects on gut movement disorders induced by loperamide. The efficacy of IAA treatment was attributable to the activation of the AHR signalling pathway and increased levels of AHR agonists. Furthermore, the oral administration of IAA-loaded nanoparticles promoted serotonin secretion and maintained the intestinal barrier function. The experimental outcomes demonstrate the efficiency of the proposed colon-specific delivery system and highlight the role of IAA, produced by gut microbiota metabolism, in regulating gut peristalsis through AHR activation.
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spelling pubmed-105746222023-10-14 Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway Chen, Ying Pan, Ruili Mei, Liya Tian, Peijun Wang, Linlin Zhao, Jianxin Chen, Wei Wang, Gang Nutrients Article Intestinal peristalsis is vital for gastrointestinal physiology and host homeostasis and is frequently dysregulated in intestinal disorders. Gut microbiota can regulate gut motility, especially through the tryptophan metabolism pathway. However, the role of indoles as microbial tryptophan metabolites in colonic function requires further exploration. Here, we show that the delivery of indole acetic acid (IAA) targeting the colon can improve gut motility by activating the aryl hydrocarbon receptor (AHR). To achieve colon-targeted delivery, Eudragit S-100 (ES) and chitosan (CS) were used as drug carriers. After optimisation, IAA-loaded ES-coated CS nanoparticles exhibited an encapsulation efficiency of 83% and a drug-loading capacity of 16%. These nanoparticles exhibited pH-dependent characteristics and remained stable in acidic conditions and the upper intestine. In simulated intestinal fluid (pH 7.4) and colonic lumen, considerable amounts of IAA were released after approximately 4 h. Compared with free IAA, the nanoparticles exerted enhanced therapeutic effects on gut movement disorders induced by loperamide. The efficacy of IAA treatment was attributable to the activation of the AHR signalling pathway and increased levels of AHR agonists. Furthermore, the oral administration of IAA-loaded nanoparticles promoted serotonin secretion and maintained the intestinal barrier function. The experimental outcomes demonstrate the efficiency of the proposed colon-specific delivery system and highlight the role of IAA, produced by gut microbiota metabolism, in regulating gut peristalsis through AHR activation. MDPI 2023-10-08 /pmc/articles/PMC10574622/ /pubmed/37836566 http://dx.doi.org/10.3390/nu15194282 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Ying
Pan, Ruili
Mei, Liya
Tian, Peijun
Wang, Linlin
Zhao, Jianxin
Chen, Wei
Wang, Gang
Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway
title Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway
title_full Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway
title_fullStr Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway
title_full_unstemmed Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway
title_short Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway
title_sort colon-targeted delivery of indole acetic acid helps regulate gut motility by activating the ahr signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574622/
https://www.ncbi.nlm.nih.gov/pubmed/37836566
http://dx.doi.org/10.3390/nu15194282
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