Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway.
Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway.
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结肠靶向递送吲哚乙酸通过激活AHR信号通路帮助调节肠道运动。
DOI：
10.3390/nu15194282
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发表时间：
2023-10-08
期刊：
影响因子：
5.9
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Chen Y;Pan R;Mei L;Tian P;Wang L;Zhao J;Chen W;Wang G
肠梗阻对于胃肠道生理和宿主体内平衡至关重要，并且在肠道疾病中经常失调。肠道微生物群可以调节肠道运动，特别是通过色氨酸代谢途径。然而，吲哚作为微生物色氨酸代谢产物在结肠功能中的作用需要进一步探索。在这里，我们表明，吲哚乙酸（IAA）靶向结肠的交付可以通过激活芳香烃受体（AHR），提高肠道运动。为了实现结肠靶向给药，使用Eudragit S-100（ES）和壳聚糖（CS）作为药物载体。优化后，IAA负载ES-涂层CS纳米粒表现出83%的包封率和载药能力的16%。这些纳米颗粒表现出pH依赖性特征，并在酸性条件下和肠道上部保持稳定。在模拟肠液（pH7.4）和结肠腔中，约4 h后释放出大量的IAA。与游离IAA相比，纳米粒对洛哌丁胺诱导的肠道运动障碍具有更强的治疗作用。IAA治疗的功效归因于AHR信号通路的激活和AHR激动剂水平的增加。此外，口服给药的IAA负载的纳米颗粒促进5-羟色胺分泌和维持肠屏障功能。实验结果证明了所提出的结肠特异性递送系统的效率，并突出了肠道微生物群代谢产生的IAA在通过AHR激活调节肠道炎症中的作用。
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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影响因子：
6.3
作者：
Sensoy I
通讯作者：
Sensoy I
肠道菌群衍生的色氨酸代谢产物调节肝细胞和巨噬细胞中的炎症反应。
影响因子：
8.8
作者：
Krishnan S;Ding Y;Saedi N;Choi M;Sridharan GV;Sherr DH;Yarmush ML;Alaniz RC;Jayaraman A;Lee K
通讯作者：
Lee K
影响因子：
9.8
作者：
Rolig AS;Mittge EK;Ganz J;Troll JV;Melancon E;Wiles TJ;Alligood K;Stephens WZ;Eisen JS;Guillemin K
通讯作者：
Guillemin K
影响因子：
64.8
作者：
Obata, Yuuki;Castano, Alvaro;Pachnis, Vassilis
通讯作者：
Pachnis, Vassilis
抗生素引起的小鼠微生物群耗竭会引起宿主血清素生物合成和肠道蠕动的变化。
影响因子：
7.4
作者：
Ge X;Ding C;Zhao W;Xu L;Tian H;Gong J;Zhu M;Li J;Li N
通讯作者：
Li N