从肠道到大脑：新加坡国立大学科学家改造细菌以治疗严重的肝性脑功能障碍

发布时间：2026-04-28来源：CISION

In vivo studies showed that programmable 'living medicines' could reduce brain toxins and prevent neurological symptoms of hepatic encephalopathy, offering distinct advantages over a widely prescribed antibiotic.

体内研究表明，可编程的“活体药物”能够减少大脑毒素并预防肝性脑病的神经症状，相较于一种广泛使用的抗生素具有明显优势。

SINGAPORE

新加坡

，

April 28, 2026

2026年4月28日

/PRNewswire/ -- When the liver fails, toxins – such as ammonia – that should be filtered from the blood build up and reach the brain. The result is hepatic encephalopathy (HE), a devastating neurological complication of liver disease that can cause anxiety, confusion, memory loss and, in severe cases, coma.

/PRNewswire/ -- 当肝脏功能衰竭时，本应从血液中过滤掉的毒素（如氨）会在体内积累并侵入大脑。其结果是肝性脑病 (HE)，这是一种由肝病引发的严重神经并发症，可能导致焦虑、意识混乱、记忆力丧失，并在严重情况下引发昏迷。

HE is a common endpoint of liver cirrhosis, driving frequent hospitalisations and placing a heavy burden on patients and healthcare systems worldwide..

肝硬化最常见的终点是肝性脑病，它导致频繁住院，并给全球患者和医疗系统带来沉重负担。

Current treatments offer only partial relief. The two mainstay therapies — lactulose and the antibiotic rifaximin — work primarily by reducing ammonia production in the gut, but neither corrects the full spectrum of metabolic disruptions that drive the disease. Patients remain vulnerable to recurrence, and rifaximin carries the added risk of disrupting the gut's natural microbiome.

目前的治疗只能提供部分缓解。两种主要的治疗方法——乳果糖和抗生素利福昔明——主要通过减少肠道中的氨生成起作用，但都无法纠正导致该疾病的全部代谢紊乱。患者仍然容易复发，而且利福昔明还存在破坏肠道天然微生物组的风险。

A fundamentally different approach is needed — one that can tackle several disease drivers at the same time..

需要一种从根本上不同的方法——一种可以同时应对多种疾病驱动因素的方法。

A research team from the

来自一个研究团队的

National University of Singapore

新加坡国立大学

(NUS), led by Professor Matthew Chang from the

（NUS），由Matthew Chang教授领导

NUS Synthetic Biology for Clinical and Technological Innovation

新加坡国立大学临床与技术创新合成生物学

(SynCTI) has recently achieved a major breakthrough on this front.

（SynCTI）近期在此方面取得了重大突破。

The researchers, who are also from the

研究人员，他们也来自

NUS Yong Loo Lin School of Medicine

新加坡国立大学杨潞龄医学院

, engineered strains of a naturally occurring beneficial gut bacterium to function as programmable therapeutics capable of restoring metabolic balance across the gut, liver and brain. The study was published in the scientific journal

，设计了天然存在的有益肠道细菌的菌株，使其成为能够在肠道、肝脏和大脑中恢复代谢平衡的可编程疗法。该研究发表在科学期刊上。

Cell

细胞

on 24 April 2026.

2026年4月24日。

Reprogramming bacteria to fight disease on multiple fronts

重新编程细菌以多管齐下对抗疾病

The researchers redesigned

研究人员重新设计了

Lactobacillus plantarum

植物乳杆菌

WCFS1 — a well-characterised commensal bacterium — into two complementary therapeutic strains. The first strain absorbs excess ammonia from the gut and converts it into branched-chain amino acids (BCAAs), essential nutrients that are depleted in HE patients. The second strain breaks down L-glutamine in the gut before it can be converted into yet more ammonia, cutting off a key source of the toxin..

WCFS1——一种特征明确的共生菌——被改造为两种互补的治疗菌株。第一种菌株吸收肠道中过多的氨，并将其转化为支链氨基酸（BCAAs），这是肝性脑病患者体内缺乏的重要营养素。第二种菌株在L-谷氨酰胺被转化为更多氨之前就将其分解，切断了这种毒素的关键来源。

Laboratory studies using a cocktail of both strains for HE showed that the combination reduced circulating ammonia by up to 10-fold and lowered brain ammonia to levels comparable to those in healthy conditions. Key metabolic imbalances — including depleted BCAAs and elevated L-glutamine — were restored, alongside marked improvements in anxiety-like symptoms and cognitive function..

使用两种菌株混合物进行的肝性脑病（HE）实验室研究表明，该组合可将循环氨水平降低多达10倍，并将脑氨降至与健康状态相当的水平。关键的代谢失衡——包括支链氨基酸（BCAAs）的减少和L-谷氨酰胺的升高——得到恢复，同时焦虑样症状和认知功能也有显著改善。

'We found that engineered gut bacteria can simultaneously remove toxic ammonia, restore essential nutrients, and improve brain-related outcomes,' explained Prof Chang. 'This directly addresses a major limitation of current treatments, which typically target only a single root cause rather than the full spectrum of metabolic drivers.'.

“我们发现工程肠道菌群可以同时去除有毒的氨，恢复必需的营养物质，并改善大脑相关的结果，”张教授解释说。“这直接解决了当前治疗的一个主要局限性，即通常只针对单一的根本原因，而不是整个代谢驱动因素的全谱。”

Distinct advantages over a front-line antibiotic

一线抗生素的显著优势

Compared with rifaximin, the engineered bacterial cocktail achieved stronger improvements in anxiety and short-term memory. In addition, neuronal signalling was normalised and neuroinflammation was reduced, suggesting gut metabolic correction can drive benefits in the central nervous system.

与利福昔明相比，工程细菌混合物在缓解焦虑和提高短期记忆方面取得了更显著的改善。此外，神经元信号传导得以正常化，神经炎症也有所减轻，这表明肠道代谢的校正可以驱动中枢神经系统的益处。

The engineered strains also preserved the natural diversity of the gut microbiome, a significant advantage over rifaximin, which markedly reduced microbial richness. In long-term safety studies, the bacteria were well tolerated, showed no signs of systemic toxicity, and were cleared within 72 hours of the final dose..

工程菌株还保留了肠道微生物组的自然多样性，相比之下，利福昔明显著降低了微生物丰富度，这是一个重要的优势。在长期安全性研究中，这些细菌耐受性良好，未表现出系统性毒性的迹象，并且在最后一次给药后 72 小时内被清除。

A platform for next-generation 'living medicines'

下一代“活体药物”平台

The team's findings point to a versatile platform for what Prof Chang calls a new class of precision therapeutics. As the bacterial strains are modular — each engineered to perform a specific metabolic task — they could be adapted to target other disorders involving the gut-liver-brain axis, including urea-cycle defects and other hyperammonaemic conditions..

该团队的研究结果指向了一个多功能平台，Chang教授称之为一类新的精准治疗药物。由于这些菌株是模块化的——每种菌株都经过工程设计以执行特定的代谢任务——它们可以被调整用于针对其他涉及肠-肝-脑轴的疾病，包括尿素循环障碍和其他高氨血症状况。

'Our study demonstrates the development of a multi-functional, programmable microbial therapy that can coordinate several therapeutic actions simultaneously inside the body,' said Prof Chang. 'Unlike standard treatments such as rifaximin, which broadly suppress gut bacteria, our approach uses live biotherapeutics to precisely reprogramme metabolism while preserving the natural gut ecosystem.'.

“我们的研究展示了一种多功能、可编程的微生物疗法的发展，它可以同时在体内协调多种治疗作用，”张教授说。“与如利福昔明等广泛抑制肠道细菌的标准治疗方法不同，我们的方法利用活体生物疗法精确地重新编程代谢，同时保留了自然的肠道生态系统。”

A patent application has been filed to support translation of the technology towards clinical use. The team's next steps include evaluating the long-term performance of the engineered strains and expanding the platform to target other diseases linked to metabolic imbalance.

团队已经申请了专利，以促进该技术向临床应用的转化。团队的下一步包括评估工程菌株的长期性能，并扩展平台以针对其他与代谢失衡相关的疾病。

'Our long-term goal is to translate this work into the clinic and develop a new class of programmable, microbe-based therapies,' added Prof Chang. 'These findings establish a strong foundation toward realising that vision.'

“我们的长期目标是将这项工作转化为临床应用，并开发一类新的可编程的、基于微生物的治疗方法，”张教授补充道。“这些发现为实现这一愿景奠定了坚实的基础。”