Yuesong Jiang, Shuaiming Jiang, Zhengting Wang, Pengfei Zhu, Jiachao Zhang, Fei Teng, Shi Huang
The human gut microbiome is a cornerstone of health, yet conventional probiotic therapies often exhibit limited efficacy owing to heterogeneity in host-microbe-environment dynamics. This review dissects the biological and environmental drivers of such variability and highlights emerging frameworks that integrate cross-sectional and longitudinal multi-omics data to predict probiotic treatment outcomes and host metabolic responses. We further spotlight breakthroughs in methodological development in efficient mining and engineering of probiotic strains, which enable the rational design of functionally enhanced, personalized probiotics. By synthesizing these advances, the review underscores the transformative potential of combining data-driven models with precision-engineered microbial therapeutics to address current limitations and usher in a new era of future microbiome-informed nutrition and personalized interventions.