人工合成益生菌群的组装策略

石语晴; 陈丹蕾; 张嘉翔; 杨艺睿; 李佳奕; 财音青格乐; 吴胜波; 乔建军

doi:10.12211/2096-8280.2025-087

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人工合成益生菌群的组装策略

特约评述 | 更新时间：2025-12-30

- 人工合成益生菌群的组装策略
- Assembly strategies for synthetic probiotic consortia
- 合成生物学 2025年页码：1-18
- 作者机构：
  
  1.天津大学合成生物与生物制造学院，天津 300350
  2.天津大学浙江研究院（绍兴），绍兴312300，浙江
  3.系统生物工程教育部重点实验室，天津大学，天津 300350
  4.合成生物技术全国重点实验室，天津大学，天津 300350
- 作者简介：
  
  [ "石语晴（2004—），女，本科在读，研究方向肠道益生菌。 E-mail：shiyuqing@tju.edu.cn" ]
  陈丹蕾（1992—），女，博士后，研究方向菌群相互作用解析、代谢交叉喂养，系统建模计算。 E-mail：danleichen@tju.edu.cn
  [ "吴胜波（1992—），男，副研究员，研究方向菌群合成生物学、菌群通信网络解析、群体感应。 E-mail：wushengbo@tju.edu.cn" ]
  [ "乔建军（1973—），男，教授，研究方向微生物合成生物学和益生菌相关功能食品相关研究。 E-mail：jianjunq@tju.edu.cn" ]
- 基金信息：
  
  国家重点研发计划“合成生物学”重点专项青年科学家项目(2024YFA0920200);国家自然科学基金(32300022)
- DOI：10.12211/2096-8280.2025-087
  中图分类号： Q816
- 收稿：2025-08-29，
  
  修回：2025-11-20，
  
  网络首发：2025-11-24，
- 稿件说明：
移动端阅览
石语晴，陈丹蕾，张嘉翔，杨艺睿，李佳奕，财音青格乐，吴胜波，乔建军. 人工合成益生菌群的组装策略［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-087

SHI Yuqing， CHEN Danlei， ZHANG Jiaxiang， YANG Yirui， LI Jiayi， CAIYIN Qinggele， WU Shengbo， QIAO Jianjun. Assembly strategies for synthetic probiotic consortia［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-087
石语晴，陈丹蕾，张嘉翔，杨艺睿，李佳奕，财音青格乐，吴胜波，乔建军. 人工合成益生菌群的组装策略［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-087 DOI：

SHI Yuqing， CHEN Danlei， ZHANG Jiaxiang， YANG Yirui， LI Jiayi， CAIYIN Qinggele， WU Shengbo， QIAO Jianjun. Assembly strategies for synthetic probiotic consortia［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-087 DOI：

摘要

人工益生菌群作为新一代合成生物学技术，在疾病干预和治疗中展现出广阔的应用前景。然而，其设计与组装方法目前尚缺乏系统性的归纳与总结。本文首先系统梳理并评析了常见益生菌单菌株在多种疾病防治中的应用现状与潜力，进而重点围绕人工益生菌群的三大组装策略展开系统综述：鸡尾酒策略、基于物理接触的互作策略以及基于小分子的非接触互作策略。鸡尾酒策略通过功能互补的菌株组合实现协同增效；物理接触策略借助基因编码黏附素、DNA介导组装及生物材料封装等技术，提升菌群定植和靶向递送能力；非接触策略则依赖群体感应系统和代谢交叉喂养策略等，实现对菌群结构和功能的精准调控。文章详细剖析了各类策略的作用设计与组装、典型应用与面临挑战，并进一步展望了多策略融合、人工智能辅助设计、临床转化等未来研究方向，为构建高效、稳定、安全的益生菌治疗体系提供理论依据和技术支撑。

Abstract

As a cutting-edge modality in synthetic biology-driven therapeutics

engineered probiotic consortia hold immense promise for disease intervention and treatment. However

the design and assembly methodologies for these synthetic ecosystems remain poorly systematized and lack comprehensive critical review. In this review

we begin by systematically reviewing and critically evaluating the current applications and therapeutic potential of common single-strain probiotics in the prevention and treatment of various diseases. Then

we provide a systematic summary for three primary assembly strategies for engineering these consortia

i.e.

the heuristic cocktail strategy

the physical contact-dependent assembly strategy

and the small molecule-mediated contact-independent assembly strategy. The heuristic cocktail approach synergizes functionally complementary bacterial strains to achieve enhanced therapeutic effects

though it faces challenges in achieving precise functional coordination and control. The physical contact-dependent assembly strategy employs techniques such as genetically encoded adhesins

DNA-programmed assembly

and biomaterial encapsulation to improve gut colonization and delivery efficiency

yet balancing colonization stability with safety remains a significant challenge. In contrast

the molecule-mediated contact-independent strategy utilizes quorum sensing and metabolic cross-feeding to achieve precise control of synthetic probiotic consortia

although the low efficiency in constructing cross-species metabolic networks presents a major bottleneck. We critically examine the mechanistic principles

representative applications

and current limitations of each strategy. Looking forward

the field is moving beyond the refinement of individual strategies toward their synergistic integration. Combining the rapid prototyping and functional complementarity of the cocktail approach with the precise spatial organization and enhanced colonization offered by physical contact-based strategies

and further empowering the consortium with the dynamic

programmable regulation afforded by molecular communication

holds the key to constructing truly robust

efficient

and intelligent therapeutic ecosystems. This integrated approach

supported by advances in artificial intelligence and genome-scale metabolic modeling

promises to accelerate the rational design of next-generation synthetic probiotics. This comprehensive overview aims to provide a foundational framework and technical reference for developing advanced

safe

and effective synthetic probiotic therapies.

关键词

Keywords

references

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