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肠道微生物群响应色氨酸和肠黏膜免疫的代谢产物:控制肠道炎症的治疗靶点。

Metabolites of microbiota response to tryptophan and intestinal mucosal immunity: A therapeutic target to control intestinal inflammation.

机构信息

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China.

Animal Husbandry and Veterinary Department, Beijing Vocational College of Agriculture, Beijing, China.

出版信息

Med Res Rev. 2021 Mar;41(2):1061-1088. doi: 10.1002/med.21752. Epub 2020 Nov 10.


DOI:10.1002/med.21752
PMID:33174230
Abstract

In a complex, diverse intestinal environment, commensal microbiota metabolizes excessive dietary tryptophan to produce more bioactive metabolites connecting with kinds of diverse process, such as host physiological defense, homeostasis, excessive immune activation and the progression and outcome of different diseases, such as inflammatory bowel disease, irritable bowel syndrome and others. Although commensal microbiota includes bacteria, fungi, and protozoa and all that, they often have the similar metabolites in tryptophan metabolism process via same or different pathways. These metabolites can work as signal to activate the innate immunity of intestinal mucosa and induce the rapid inflammation response. They are critical in reconstruction of lumen homeostasis as well. This review aims to seek the potential function and mechanism of microbiota-derived tryptophan metabolites as targets to regulate and shape intestinal immune function, which mainly focused on two aspects. First, analyze the character of tryptophan metabolism in bacteria, fungi, and protozoa, and assess the functions of their metabolites (including indole and eight other derivatives, serotonin (5-HT) and d-tryptophan) on regulating the integrity of intestinal epithelium and the immunity of the intestinal mucosa. Second, focus on the mediator and pathway for their recognition, transfer and crosstalk between microbiota-derived tryptophan metabolites and intestinal mucosal immunity. Disruption of intestinal homeostasis has been described in different intestinal inflammatory diseases, available data suggest the remarkable potential of tryptophan-derived aryl hydrocarbon receptor agonists, indole derivatives on lumen equilibrium. These metabolites as preventive and therapeutic interventions have potential to promote proinflammatory or anti-inflammatory responses of the gut.

摘要

在复杂多样的肠道环境中,共生微生物群将过量的膳食色氨酸代谢为更多具有生物活性的代谢物,这些代谢物与多种不同的过程相关联,如宿主生理防御、内稳态、过度免疫激活以及各种疾病的进展和结果,如炎症性肠病、肠易激综合征等。尽管共生微生物群包括细菌、真菌和原生动物等,但它们在色氨酸代谢过程中经常通过相同或不同的途径产生相似的代谢物。这些代谢物可以作为信号激活肠道黏膜的先天免疫,并诱导快速炎症反应。它们在腔室的动态平衡重建中也很重要。本综述旨在探讨微生物衍生色氨酸代谢物作为调节和塑造肠道免疫功能的靶点的潜在功能和机制,主要集中在两个方面。首先,分析细菌、真菌和原生动物中色氨酸代谢的特点,并评估其代谢物(包括吲哚和其他八种衍生物、血清素 (5-HT) 和 d-色氨酸)在调节肠道上皮完整性和肠道黏膜免疫方面的功能。其次,关注它们的识别、转移以及微生物衍生色氨酸代谢物与肠道黏膜免疫之间的串扰的介质和途径。肠道内稳态的破坏已在不同的肠道炎症性疾病中描述,现有数据表明,色氨酸衍生的芳香烃受体激动剂、吲哚衍生物对腔平衡具有显著的潜力。这些代谢物作为预防和治疗干预措施具有促进肠道促炎或抗炎反应的潜力。

相似文献

[1]
Metabolites of microbiota response to tryptophan and intestinal mucosal immunity: A therapeutic target to control intestinal inflammation.

Med Res Rev. 2021-3

[2]
Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism.

Front Cell Infect Microbiol. 2018-2-6

[3]
Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation.

Front Immunol. 2021

[4]
Tryptophan and the innate intestinal immunity: Crosstalk between metabolites, host innate immune cells, and microbiota.

Eur J Immunol. 2022-6

[5]
Manipulation of epithelial integrity and mucosal immunity by host and microbiota-derived metabolites.

Eur J Immunol. 2020-6-28

[6]
Gut microbiota-derived tryptophan metabolism mediates renal fibrosis by aryl hydrocarbon receptor signaling activation.

Cell Mol Life Sci. 2021-2

[7]
The Aryl Hydrocarbon Receptor (AHR) as a Potential Target for the Control of Intestinal Inflammation: Insights from an Immune and Bacteria Sensor Receptor.

Clin Rev Allergy Immunol. 2020-12

[8]
The Impact of Dietary Sphingolipids on Intestinal Microbiota and Gastrointestinal Immune Homeostasis.

Front Immunol. 2021

[9]
Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis.

Cells. 2022-7-25

[10]
The aryl hydrocarbon receptor as a mediator of host-microbiota interplay.

Gut Microbes. 2020-11-9

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Gut Microbiota-Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers.

FASEB J. 2025-9-15

[2]
From Microbial Switches to Metabolic Sensors: Rewiring the Gut-Brain Kynurenine Circuit.

Biomedicines. 2025-8-19

[3]
TDO-mediated tissue-specific regulation of kynurenine pathway in the brain and gill of Litopenaeus vannamei.

BMC Genomics. 2025-8-26

[4]
Lactiplantibacillus plantarum attenuate gossypol-induced hepatic lipotoxicity by altering intestinal microbiota for enriching microbial tryptophan metabolites in Nile tilapia (Oreochromis niloticus).

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[5]
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Front Pharmacol. 2025-6-10

[6]
Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis suppressing IL-13R1 related signaling pathways.

Acta Pharm Sin B. 2025-4

[7]
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Front Endocrinol (Lausanne). 2025-5-22

[8]
Butyrate alleviates food allergy by improving intestinal barrier integrity through suppressing oxidative stress-mediated Notch signaling.

Imeta. 2025-4-3

[9]
Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease.

Cell Mol Immunol. 2025-5-21

[10]
Association between AHR in EGCs and IBS-D patients: the indole pathway of tryptophan metabolism.

Front Nutr. 2025-3-28

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