A Review of Probiotic Intervention Targets in Diseases: Unveiling Mechanisms and Providing Insights toward Engineering Strategies

Rapid advances in gut microbiota research have revealed that probiotics have an indispensable impact on the prevention and alleviation of a wide range of diseases. However, no genetically based engineering techniques have been reported because the targets and regulated genes associated with probiotics in these diseases have not been systematically discussed. This article provides an overview of the relationship between probiotics, including probiotic species and gene technologies, and contemporary disease targets. It also discusses the related disease therapeutic mechanisms. From the perspective of genetic composition, based on these targets and probiotic properties, current probiotic engineering strategies and new strategies with new technologies have been proposed. Probiotics have specific effects on multiple disease targets, including metabolites, membrane structures, and host immune stimulation. To enhance the advantages of probiotics, various engineering strategies targeting disease targets should be systematically summarized, including probiotic breeding and domestication, membrane protein research, and gene editing technology. Additionally, this review suggests novel approaches for engineering probiotics, such as spatial omics technology, Alpha-fold3 prospective applications, and modeling technology. This review reveals the mechanisms of probiotic intervention in diseases and proposes new engineering strategies and research concepts for disease targets.