Gene Editing in Livestock: Bridging Gut Microbiome Modulation and Antibiotic Resistance Mitigation

The crisis of antibiotic resistance caused by the overuse of antibiotics has become a major threat to global agriculture and public health, and traditional livestock strategies have demonstrated significant limitations in addressing this challenge. Gene editing technologies, in particular the CRISPR-Cas9 system, offer innovative solutions to the problem of antibiotic resistance by regulating the gut microbiota of livestock and directly interfering with resistance genes. This study systematically explores cross-cutting applications of gene editing technology in livestock health management, focusing on three major themes: (1) Editing host genes to optimize gut microbiota balance; (2) Directly editing resistant genes of pathogenic bacteria to restore their sensitivity to antibiotics; (3) Developing collaborative strategies (phage delivery systems and probiotic engineering). The results showed that pigs with CD163 gene knocked out by CRISPR-Cas9 had complete resistance to porcine reproductive and respiratory syndrome. Engineered probiotics can remove 99.9% of resistant bacteria; The bifunctional delivery strategy reduced the intestinal drug-resistant bacterial load to <100 CFU/g. In addition, multi-omics techniques provide a precise tool for dynamically assessing the effects of gene editing on microbiome function. Conclusion: Through the new strategy of "host-microbiome co-editing", gene editing technology has the potential to be transformative in livestock microbiome regulation and drug resistance management, but challenges such as delivery efficiency, ecological risks and ethical controversies still need to be addressed, and its widespread application depends on technological innovation, interdisciplinary cooperation and the coordinated development of an international regulatory framework. To achieve the dual goals of agricultural sustainability and public health security.