新加坡国立大学Matthew Wook Chang团队开发出了工程化共生菌，用于靶向鼻腔到大脑的药物递送。这一研究成果发表在2025年2月5日出版的国际学术期刊《细胞》上。

在这项研究中，研究人员鉴定了植物乳杆菌WCFS1 (Lp)，这是一种与嗅上皮具有天然亲和力的共生菌株，并将其改造为脑药物传递载体。经鼻给药后，植物乳杆菌在嗅上皮内释放特定的有效载荷分子，随后在大脑中运输和积累。

通过重组产生和分泌食欲调节激素，进一步验证了植物乳杆菌的治疗效果。在预防肥胖的小鼠模型中，经鼻给药后，工程化的植物乳杆菌显著减轻了肥胖相关症状。这表现为食欲下降、体重增加减少、葡萄糖代谢改善和脂肪质量沉积减少。

他们的研究证明了植物乳杆菌作为鼻内递送载体的能力，强调了其在脑靶向治疗应用方面的潜力。

据了解，通过嗅上皮（OE）鼻内给药为脑靶向治疗提供了一条直接途径，尽管其可行性受到嗅上皮解剖和吸收限制的阻碍。

附：英文原文

Title: Engineered commensals for targeted nose-to-brain drug delivery

Author: Haosheng Shen, Nikhil Aggarwal, Beiming Cui, Guo Wei Foo, Yuanzhi He, Santosh Kumar Srivastava, Shengjie Li, Marcus Ze Xian Seah, Kwok Soon Wun, Hua Ling, In Young Hwang, Chun Loong Ho, Yung Seng Lee, Matthew Wook Chang

Issue&Volume: 2025-02-05

Abstract: Intranasal administration through the olfactory epithelium (OE) presents a direct pathway for brain-targeted therapeutic delivery, although its feasibility is hampered by the anatomical and absorptive limitations of the OE. In this study, we identified Lactobacillus plantarum WCFS1 (Lp), a commensal strain with a natural affinity for the OE and engineered it to function as a vector for cerebral drug delivery. Upon intranasal administration, Lp released specific payload molecules within the OE, with subsequent transport and accumulation in the brain. The therapeutic efficacy of Lp was further validated by the recombinant production and secretion of appetite-regulating hormones. When administered intranasally in a murine model of obesity prevention, the engineered Lp significantly alleviated obesity-related symptoms. This was evidenced by decreased appetite, reduced body weight gain, and improved glucose metabolism and fat mass deposition. Our study demonstrates the capability of Lp as an intranasal delivery vehicle, emphasizing its potential for brain-targeted therapeutic applications.

DOI: 10.1016/j.cell.2025.01.017

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00046-7