Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity.
Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity.
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肠道微生物衍生的色氨酸代谢物是Ah受体活性的预测。
DOI：
10.1080/19490976.2020.1788899
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Perdew GH
中科院分区：
文献类型：
--
作者：
Dong F;Hao F;Murray IA;Smith PB;Koo I;Tindall AM;Kris-Etherton PM;Gowda K;Amin SG;Patterson AD;Perdew GH
胃肠道内依赖共生微生物区系的色氨酸分解代谢对宿主生理产生深远影响，包括维持上皮屏障和免疫功能。大量微生物衍生的色氨酸代谢物对芳香烃受体(AHR)具有激活潜力。AHR通过饮食或微生物产生的代谢物的存在促进了基因的表达，可以影响胃肠道的动态平衡，并提供对肠道挑战的保护。利用基于非靶向质谱学的代谢组学分析，结合AHR活性筛选分析，我们确定了四种先前未识别的色氨酸代谢物，存在于小鼠盲肠内容物和人类粪便中，具有激活AHR的能力。利用GC/MS和LC/MS平台，实现了对这些新的AHR激活剂以及先前建立的AHR激活色氨酸代谢物的定量，提供了相对丰度的顺序。利用生理相关浓度和定量基因表达分析，检验了这些色氨酸代谢物对小鼠或人类AHR激活潜力的相对有效性。这些数据显示，吲哚、2-氧吲哚、吲哚-3-乙酸和犬尿酸是受试者在控制饮食的小鼠盲肠内容物和人类粪便中的主要AHR激活剂。在这里，我们提供了一组微生物衍生的色氨酸代谢物的相对丰度和AHR激活潜力的第一份文件。此外，这些数据表明，在生理上相关的浓度下，人的AHR对色氨酸代谢物的激活比小鼠的AHR更敏感。此外，相关分析表明，主要色氨酸代谢物丰度与AHR活性之间存在联系，表明这些盲肠/粪便代谢物是肠道AHR活性的生物标志物。
Commensal microbiota-dependent tryptophan catabolism within the gastrointestinal tract is known to exert profound effects upon host physiology, including the maintenance of epithelial barrier and immune function. A number of abundant microbiota-derived tryptophan metabolites exhibit activation potential for the aryl hydrocarbon receptor (AHR). Gene expression facilitated by AHR activation through the presence of dietary or microbiota-generated metabolites can influence gastrointestinal homeostasis and confer protection from intestinal challenges. Utilizing untargeted mass spectrometry-based metabolomics profiling, combined with AHR activity screening assays, we identify four previously unrecognized tryptophan metabolites, present in mouse cecal contents and human stool, with the capacity to activate AHR. Using GC/MS and LC/MS platforms, quantification of these novel AHR activators, along with previously established AHR-activating tryptophan metabolites, was achieved, providing a relative order of abundance. Using physiologically relevant concentrations and quantitative gene expression analyses, the relative efficacy of these tryptophan metabolites with regard to mouse or human AHR activation potential is examined. These data reveal indole, 2-oxindole, indole-3-acetic acid and kynurenic acid as the dominant AHR activators in mouse cecal contents and human stool from participants on a controlled diet. Here we provide the first documentation of the relative abundance and AHR activation potential of a panel of microbiota-derived tryptophan metabolites. Furthermore, these data reveal the human AHR to be more sensitive, at physiologically relevant concentrations, to tryptophan metabolite activation than mouse AHR. Additionally, correlation analyses indicate a relationship linking major tryptophan metabolite abundance with AHR activity, suggesting these cecal/fecal metabolites represent biomarkers of intestinal AHR activity.
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影响因子：
7.4
作者：
Koo, Imhoi;Zhang, Xiang;Kim, Seongho
通讯作者：
Kim, Seongho
影响因子：
4.6
作者：
Hubbard TD;Murray IA;Bisson WH;Lahoti TS;Gowda K;Amin SG;Patterson AD;Perdew GH
通讯作者：
Perdew GH
影响因子：
3.6
作者：
Flaveny, Colin A.;Murray, Iain A.;Perdew, Gary H.
通讯作者：
Perdew, Gary H.
DOI：
10.33594/000000209
发表时间：
2020-02-05
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Manzella, Christopher R;Ackerman, Max;Gill, Ravinder K
通讯作者：
Gill, Ravinder K
影响因子：
3.6
作者：
Long, WP;Pray-Grant, M;Perdew, GH
通讯作者：
Perdew, GH