Designer probiotic-based living drugs for uric acid homeostasis control in hyperuricemic mice and rats.

IF 10.6 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-10-01 DOI:10.1016/j.xcrm.2025.102379

Xianyun Gao, Yiyu Jin, Mengyao Liu, Wenbo Ma, Deqiang Kong, Yang Zhou, Lingxue Niu, Jianli Yin, Haibing Chen, Haifeng Ye, Ningzi Guan

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Abstract

Engineered probiotics can effectively manage hyperuricemia, a condition characterized by increased serum uric acid (UA) levels, leading to several chronic diseases. In this study, we design a probiotic-based UA level sensing and adjustment (PULSE)-engineered bacterium to maintain UA homeostasis. We generate a UA sensor in the E. coli Nissle 1917 strain based on a UA-responsive transcriptional repressor HucR, integrated with a synthetic promoter. Upon oral administration of engineered probiotics, PULSE cells dynamically regulate urate oxidase expression, reducing UA in the gastrointestinal tract in response to increased serum levels. We have demonstrated the potential of PULSE-engineered bacteria in maintaining UA balance in acute and chronic hyperuricemic mouse and rat models, highlighting the potential for long-term oral administration in reducing hyperuricemia-associated renal damage. Our probiotic-based living drug supports the progress of engineered probiotics as a safe, effective, and patient-friendly alternative to typical therapeutics for chronic disease management.

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基于益生菌的高尿酸血症小鼠和大鼠尿酸稳态控制活性药物设计。

工程益生菌可以有效地控制高尿酸血症，这是一种以血清尿酸（UA）水平升高为特征的疾病，导致几种慢性疾病。在这项研究中，我们设计了一种基于益生菌的UA水平传感和调节（PULSE）工程细菌来维持UA的稳态。我们在大肠杆菌Nissle 1917菌株中生成了一个UA传感器，该传感器基于一个UA响应转录抑制因子HucR，与一个合成启动子集成。口服工程益生菌后，PULSE细胞动态调节尿酸氧化酶的表达，降低胃肠道中的尿酸水平，以响应血清水平的升高。我们已经证明了脉冲工程细菌在维持急性和慢性高尿酸血症小鼠和大鼠模型中的UA平衡方面的潜力，强调了长期口服给药在减少高尿酸血症相关肾损害方面的潜力。我们以益生菌为基础的活性药物支持了工程益生菌作为一种安全、有效和对患者友好的慢性疾病治疗的典型替代疗法的进展。

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

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.