Jiang, X.; Hou, J.; Zhang, H.; Guo, J.; Gu, S.; Vandeputte, D.; Liao, Y.; Guo, Q.; Yang, X.; Zhou, Y.; Geng, P. X.; Wang, C.; Li, M.; Jousset, A.; Shen, X.; Wei, Z.; Zhu, H.

Designing microbial communities to generate target products is crucial for biotechnology, agriculture, and disease treatment. However, rationally designing such communities from large seed pools has become a major challenge, as the rapidly expanding number of complete microbial genomes greatly expands the search space and sharply increases the required screening time and computational cost. Here, we introduce eBiota, a platform for ab initio design of microbial communities from a pool of 21,514 strains to generate target products. eBiota not only identifies optimal strain combinations but also simulates community behaviors, including microbial interactions and relative abundances. eBiota integrates three modules: CoreBFS, a graph-based search algorithm that rapidly screens for bacteria with complete metabolic pathways related to the target product; ProdFBA, an extended flux balance analysis that identifies microbial consortia with maximal production efficiency; and DeepCooc, a deep learning model trained on 23,323 microbiome samples across various environments to infer co-occurrence patterns. We validated eBiota's capabilities in microbial community design and production efficiency calculation using public microbiome datasets, ranging from single strains to six-member consortia. Further in vitro experiments involving 94 strains confirmed eBiota's ability to identify species that inhibit pathogen growth and to accurately model the relative abundances within complex microbial communities. As an initial digital twin, eBiota provides a powerful platform for the rational design of functional microbial communities, offering new opportunities for metabolic engineering and synthetic biology.