The Tryptophan-Kynurenine pathway in people living with HIV: a systematic review.

IF 5.4 2区医学 Q1 INFECTIOUS DISEASES

Infection Pub Date : 2025-05-31 DOI:10.1007/s15010-025-02557-1

Tshiamo Will Sebigi, Levanco K Asia, Grant G January, Esmé Jansen van Vuren, Monray Edward Williams

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引用次数: 0

Abstract

Purpose: HIV-1 disrupts the metabolic profile of people living with HIV (PLWH), including the Tryptophan-Kynurenine (Trp-Kyn) pathway, linked to disease outcomes and comorbidities. Despite numerous studies, consensus on key dysregulated metabolites in antiretroviral therapy (ART)-treated PLWH is lacking. This systematic review compiles data to identify and highlight the most noteworthy Trp-Kyn metabolites.

Methods: PubMed, Scopus, and Web of Science databases were searched using a search protocol specifically designed for this study. Studies that investigated the levels of metabolites in the Trp-Kyn pathway in the peripheral blood of PLWH on ART, as well as in healthy control groups were included.

Results: Thirteen metabolomic studies that investigated this pathway met our inclusion criteria. The findings revealed that Trp, Kyn, and the Kyn/Trp ratio (indicative of indoleamine 2,3-dioxygenase IDO activity) were the most investigated metabolites in this metabolic pathway. Evidence consistently demonstrated that Trp levels were lower in PLWH, while predicted IDO activity was consistently higher. Despite the widespread investigation of Kyn, there was no clear consensus on its levels in PLWH, with some studies reporting higher levels and others finding no significant differences compared to HIV-negative controls.

Conclusion: In the modern ART era, Trp metabolism and IDO activity may play key regulatory roles in HIV-1 pathogenesis, as evidenced by the consistent patterns observed across various studies. These metabolites and related pathways warrant further investigation as potential targets for improved diagnostics, prognostics, and therapeutics in the context of HIV-1.

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HIV感染者的色氨酸-犬尿氨酸途径：一项系统综述。

目的：HIV-1破坏HIV感染者（PLWH）的代谢谱，包括与疾病结局和合并症相关的色氨酸-犬尿氨酸（Trp-Kyn）途径。尽管进行了大量的研究，但对抗逆转录病毒治疗（ART）治疗的PLWH中关键的失调代谢物缺乏共识。本系统综述汇编了数据，以识别和突出最值得注意的Trp-Kyn代谢物。方法：使用专门为本研究设计的搜索协议对PubMed、Scopus和Web of Science数据库进行检索。研究包括抗逆转录病毒治疗的PLWH外周血中Trp-Kyn通路代谢物水平，以及健康对照组。结果：13项研究这一途径的代谢组学研究符合我们的纳入标准。结果表明，Trp、Kyn和Kyn/Trp比值（表明吲哚胺2,3-双加氧酶IDO活性）是该代谢途径中研究最多的代谢物。证据一致表明，PLWH中的Trp水平较低，而预测的IDO活性始终较高。尽管对Kyn进行了广泛的调查，但对其在PLWH中的水平没有明确的共识，一些研究报告的水平较高，而另一些研究发现与hiv阴性对照相比没有显著差异。结论：在现代ART时代，Trp代谢和IDO活性可能在HIV-1发病机制中发挥关键调节作用，各种研究观察到的一致模式证明了这一点。这些代谢物和相关途径值得进一步研究，作为改进HIV-1诊断、预后和治疗的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infection 医学-传染病学

CiteScore

12.50

自引率

1.30%

发文量

224

审稿时长

6-12 weeks

期刊介绍： Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings. The journal covers a wide range of topics, including: Etiology: The study of the causes of infectious diseases. Pathogenesis: The process by which an infectious agent causes disease. Diagnosis: The methods and techniques used to identify infectious diseases. Treatment: The medical interventions and strategies employed to treat infectious diseases. Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies. Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections. In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.