合成微生物组的理性设计与构建范式演进

Rational design and paradigm shifts in synthetic microbiomes

摘要:

天然微生物组的应用受限于其组成复杂、功能难以调控，因此合成微生物组成为微生物组工程的核心方向。早期二元合成微生物组在受控条件下能够实现功能协同，但在真实复杂环境中由于代谢单一、冗余不足，其稳定性与功能持久性较差。近年来，合成微生物组研究从经验驱动转向理性设计，在菌株资源获取、构建策略(“自上而下” “自下而上”及混合范式)以及计算工具(如基因组尺度代谢模型)等方面取得进展。然而，现有研究框架对复杂环境下群落的稳定性、鲁棒性及生态互作的重视不足。本文梳理了合成微生物组构建范式的演进脉络，评述了增强群落稳定性的关键要素，通过构建多层次代谢网络提升其在复杂环境中的功能持续性与鲁棒性。展望未来，需整合多学科技术，推动工程化微生物组向可预测、长期稳定的方向转变，为构建高鲁棒性合成微生物组提供理论框架与研究方向。

Abstract:

The application of natural microbiomes is limited by their complex composition and uncontrollable functions, which makes synthetic microbiomes a core direction in microbiome engineering. Early binary synthetic microbiomes can achieve functional synergy under controlled conditions, whereas they exhibit poor stability and limited functional persistence in real complex environments due to their simple metabolic pathways and insufficient ecological redundancy. In recent years, the research on synthetic microbiomes has shifted from an empirically driven approach to rational design, achieving significant progress in strain resource acquisition, construction strategies (top-down, bottom-up, and their hybrid paradigms), and computational tools (e.g., genome-scale metabolic models). However, current design frameworks still focus primarily on functional realization, with insufficient attention paid to the long-term stability, system robustness, and multi-level ecological interactions of communities in complex environments. This paper systematically sorts out the evolutionary trajectory of synthetic microbiome construction paradigms and reviews the key elements for enhancing community stability. By establishing a multi-level metabolic network, this paradigm significantly improves the functional persistence and ecological robustness of synthetic microbiomes in complex and fluctuating environments. The future research on synthetic microbiomes needs to further integrate multidisciplinary technologies to improve the predictability and long-term stability of engineered microbiomes, providing a systematic theoretical framework and research directions for constructing highly robust synthetic microbiomes.