How can microbiomes be rationally designed？ Bridging the gaps from interaction mechanisms to microbiome engineering

JIN Xiao; WANG Miaoxiao

doi:10.12211/2096-8280.2026-031

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How can microbiomes be rationally designed？ Bridging the gaps from interaction mechanisms to microbiome engineering

更新时间：2026-07-31

- How can microbiomes be rationally designed？ Bridging the gaps from interaction mechanisms to microbiome engineering
- 微生物组如何被理性设计？——从互作机制解析到工程微生物组构建的关键缺环与未来展望
- Synthetic Biology Journal Pages: 1-30(2026)
- 作者机构：
  
  电子科技大学基础与前沿研究院，四川成都　611731
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2026-031
  CLC： Q815;Q938.1
- Received：29 April 2026，
  
  Revised：2026-07-28，
  
  Online First：31 July 2026，
- 稿件说明：
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金潇，王淼啸. 微生物组如何被理性设计？——从互作机制解析到工程微生物组构建的关键缺环与未来展望［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-031

JIN Xiao， WANG Miaoxiao. How can microbiomes be rationally designed？ Bridging the gaps from interaction mechanisms to microbiome engineering［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-031
金潇，王淼啸. 微生物组如何被理性设计？——从互作机制解析到工程微生物组构建的关键缺环与未来展望［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-031 DOI：

JIN Xiao， WANG Miaoxiao. How can microbiomes be rationally designed？ Bridging the gaps from interaction mechanisms to microbiome engineering［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-031 DOI：

摘要

微生物群落广泛存在于自然与工程环境中，驱动着复杂的物质转化与生物地球化学循环，展现出多样且高效的功能。基于此发展出的微生物组工程理论和方法，为环境修复、农业生产与生物制造等领域提供了新的技术路径。近年来，大量研究已在低复杂度合成群落中解析了基于代谢交叉喂养、代谢分工等典型互作关系的群落调控机制。然而，这些机制多建立在理想化、低维度体系下，其适用范围与普适性仍有待验证，尤其是在向复杂工程微生物组外推时，缺乏系统性的设计原则。同时，工程微生物组应用场景通常处于动态变化中，微生物间相互作用亦随环境波动、时空尺度和物种流动发生动态变化，使得基于静态与封闭体系获得的机制难以直接用于复杂体系的预测与设计。基于此，本文围绕微生物互作机制解析如何向复杂工程微生物组设计转化的关键问题，回顾了典型互作机制在理想体系中的研究进展，分析了其在向复杂微生物组外推过程中的重要缺环。本文进一步重点讨论了互作机制跨时间与空间尺度放大中的主要挑战，并梳理了环境波动、开放体系中迁入迁出等因素对互作关系及群落动态的调控作用。在此基础上，本文指出，未来需拓展从两两互作向高阶互作的研究，发展基于机制分类与标准化参数的定量表征框架，并构建跨时空尺度的预测模型；提出应在动态与开放情境中解析互作机制，并建立面向工程应用的鲁棒性测试体系，以提升工程微生物组设计原理的可预测性与可迁移性。

Abstract

Microbial communities are ubiquitous in both natural and engineered environments

where they drive complex biotransformations and biogeochemical cycles and exhibit diverse and efficient functional outputs. Building on these properties

microbiome engineering has emerged as a promising framework for applications in environmental remediation

agriculture

and biomanufacturing. In recent years

extensive efforts have elucidated key regulatory mechanisms in low-complexity synthetic communities

particularly those mediated by metabolic cross-feeding and metabolic division of labor. However

these mechanisms are largely derived from idealized and low-dimensional systems

and their applicability and generalizability remain to be validated

especially when extrapolated to complex engineered microbiomes

where systematic design principles are still lacking. Moreover

engineered microbiomes typically operate under dynamic conditions

in which microbial interactions are continuously reshaped by environmental fluctuations

spatiotemporal heterogeneity

and species immigration and emigration. As a result

mechanisms derived from static and closed systems are difficult to directly apply to the prediction and design of complex microbiome systems. In this context

this review focuses on the critical challenge of translating mechanistic insights into microbiome interactions into the rational design of complex engineered microbiomes. We summarize recent advances in understanding canonical interaction mechanisms in simplified systems and analyze the key gaps that limit their extrapolation to complex communities. We further discuss the major challenges associated with scaling interaction mechanisms across temporal and spatial dimensions

and review how environmental fluctuations and species turnover in open systems regulate microbial interactions and community dynamics. Based on these insights

we highlight the need to extend studies from pairwise to higher-order interactions

to develop quantitative frameworks based on mechanistic classification and standardized parameters

and to construct predictive models across spatiotemporal scales. We also propose that interaction mechanisms should be investigated under dynamic and open conditions

and that robustness-testing frameworks tailored to engineering applications should be established to enhance the predictability and transferability of microbiome design principles.

关键词

Keywords

references

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QIAO Jianjun

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School of Synthetic Biology and Biomanufacturing， Tianjin University

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State Key Laboratory of Synthetic Biology， Tianjin University

State Key Laboratory of Animal Nutrition and Feeding， Institute of Animal Sciences， Chinese Academy of Agricultural Sciences

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