Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases

IF 15.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI:10.1016/j.arr.2026.103036

Nan Chen , Carmen K. Chan , Farhan Ullah Khan , Priya Makhijani , Taylor R. Valentino , Shawn Winer , Cynthia T. Luk , Daniel A. Winer

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Abstract

Age-associated dysbiosis, marked by shifts in the composition of gut microbiota and gut microbiota-derived metabolites (GMDMs), is increasingly implicated in driving systemic low-grade inflammation during aging. The disrupted GMDM pools, including altered levels of short-chain fatty acids (SCFAs), secondary bile acids (BAs) and tryptophan (Trp) metabolites, lead to mucosal barrier dysfunction, immunometabolic dysregulation, and modulation of innate and adaptive immune cells. In turn, this cascade of events drives tissue degeneration, chronic inflammation, and the onset of age-related diseases (ARDs). Here, we summarize the immunomodulatory role of major GMDMs and how aging may increase susceptibility to ARDs through changing GMDMs. We then explore the latest findings linking altered GMDM profiles to immune dysfunction across major gut-organ axes, including the liver, adipose tissue, muscle, and brain. Last, we highlight recent advances in harnessing GMDMs as geromedicine to improve aging parameters and discuss the potential of artificial intelligence (AI) in accelerating the bench-to-bedside translation of GMDM research. Together, this review positions GMDMs as actionable targets in a dysbiosis-driven network of immune aging, offering new possibilities for the development of healthspan-extending precision geromedicine.

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肠道微生物衍生代谢物在衰老和年龄相关慢性炎症疾病中的免疫调节剂作用

以肠道菌群和肠道菌群衍生代谢物（GMDMs）组成变化为标志的与年龄相关的生态失调，越来越多地与衰老过程中驱动全身性低度炎症有关。GMDM池的破坏，包括短链脂肪酸（SCFAs）、次级胆油酸（BAs）和色氨酸（Trp）代谢物水平的改变，导致粘膜屏障功能障碍、免疫代谢失调以及先天和适应性免疫细胞的调节。反过来，这一连串的事件驱动组织退化、慢性炎症和年龄相关疾病（ARDs）的发作。在这里，我们总结了主要gmdm的免疫调节作用，以及衰老如何通过改变gmdm增加ARDs的易感性。然后，我们探索了将GMDM的改变与主要内脏器官轴（包括肝脏、脂肪组织、肌肉和大脑）的免疫功能障碍联系起来的最新发现。最后，我们强调了利用GMDM作为基因医学来改善衰老参数的最新进展，并讨论了人工智能（AI）在加速GMDM研究从实验室到临床转化方面的潜力。总之，本综述将gmdm定位为生态失调驱动的免疫衰老网络中可操作的靶点，为发展延长健康寿命的精准老年医学提供了新的可能性。

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

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.