Microbiome editing in infectious disease prevention and therapy: CRISPR Applications in Host-Microbe Interactions

The advent of CRISPR-Cas systems has redefined the frontiers of microbiome engineering, offering unprecedented precision in modulating host-microbe interactions for the prevention and treatment of infectious diseases. This article explores the revolutionary potential of microbiome editing, focusing on the deployment of CRISPR-based technologies to restore microbial balance, suppress pathogenicity, and enhance host immunity. It traces the limitations of traditional microbiome modulation methods—such as probiotics, prebiotics, and fecal microbiota transplantation—and contrasts them with the unparalleled specificity and adaptability of CRISPR-guided interventions. Key applications include the in situ editing of commensal and pathogenic bacteria, the development of programmable antimicrobials targeting antibiotic resistance, and the engineering of probiotics to deliver targeted therapeutic payloads. Through case studies involving Clostridioides difficile and Salmonella spp., the article demonstrates real-world feasibility and therapeutic promise. Additionally, it addresses the systemic influence of the gut microbiota on distant organ systems via the gut-lung, gut-brain, and gut-immune axes, underscoring the relevance of microbiome-targeted therapies in conditions such as sepsis, respiratory infections, and HIV. The paper critically evaluates the delivery mechanisms of CRISPR constructs—spanning phage vectors, conjugative plasmids, and nanoparticles—while navigating the ethical, ecological, and regulatory landscapes that frame this emerging field. By integrating recent scientific advances with translational insights, this review establishes microbiome editing not merely as a futuristic concept, but as a transformative strategy poised to redefine the clinical management of infectious and systemic diseases.