[Synthetic microbiomes: rational design, engineering strategies, and application prospects]

Microbiomes in natural environments have diverse functions and harbor vast exploitable potential of modifying the nature and hosts, being significant resources for development. The inherent high complexity and uncontrollability of natural microbiomes, as well as the selection by the nature and hosts, impose significant constraints on practical applications. Synthetic microbiomes, serving as precisely defined engineered microbiomes, demonstrate enhanced functionality, stability, and controllability compared with natural microbiomes. These engineered microbiomes emerge as a prominent research focus and are potentially having applications across various fields including environmental bioremediation and host health management. Nevertheless, substantial challenges persist in both fundamental research and practical application of synthetic microbiomes. This review systematically summarizes three core design principles for synthetic microbiomes, introduces current construction strategies including top-down, bottom-up, and integrated approaches, and comprehensively lists their applications in environmental remediation, agricultural innovation, industrial biotechnology, and healthcare. Furthermore, it critically examines existing technical and conceptual challenges while proposing strategic recommendations, thereby providing theoretical guidance for future advancements in the design, engineering, and application of synthetic microbiomes.