Amen Radwa A, Hassan Yaser M, Essmat Rawan A, Ahmed Rana H, Azab Marwan M, Shehata Nadia R, Elgazzar Mariam M, El-Sayed Wael M
Department of Biotechnology, Faculty of Science, Cairo University, Cairo, Egypt.
Biotechnology Program, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
Probiotics Antimicrob Proteins. 2025 May 16. doi: 10.1007/s12602-025-10573-8.
The growing crisis of antibiotic resistance and the increasing incidence of cancer have prompted the exploration of innovative approaches, such as gene editing and antimicrobial peptides (AMPs). The human microbiome is integral to various aspects of health, disease, and therapeutic development, influencing metabolic pathways, immune function, and pathogen resistance. Recent advances in gene editing technologies, particularly CRISPR (clustered regularly interspaced short palindromic repeats), have opened new avenues for leveraging the microbiome to address complex medical challenges, including combating multidrug-resistant pathogens and cancer. The microbiome plays a crucial role in combating antibiotic resistance by modulating microbial communities, influencing pathogen survival and susceptibility to treatments. This review explores the microbiome's dynamic role in metabolic regulation, its contribution to cancer management, and how AMPs help maintain homeostasis and exhibit emerging anticancer properties, supported by both preclinical findings and clinical evidence. Additionally, CRISPR-based microbiome engineering offers potential to enhance host-microbiome interactions, optimizing therapeutic outcomes. The integration of microbiome metagenomics and proteomics has led to the discovery of novel AMPs with targeted anticancer effects. Innovative strategies, such as engineered probiotics and CRISPR-based microbiome engineering, present exciting prospects for next-generation therapies. Despite these advances, the translation of microbiome-based therapies into clinical settings remains challenging due to ethical, regulatory, and ecological hurdles. This review underscores the transformative potential of microbiome-based interventions, emphasizing the role of personalized medicine in maximizing therapeutic efficacy. Furthermore, we also address critical research gaps, limitations, and future directions, including optimizing AMP stability, delivery, and bioavailability, as well as overcoming the regulatory and ethical challenges in clinical translation.
抗生素耐药性危机的不断加剧以及癌症发病率的日益上升,促使人们探索创新方法,如基因编辑和抗菌肽(AMPs)。人类微生物群对于健康、疾病及治疗发展的各个方面都至关重要,影响着代谢途径、免疫功能和病原体抗性。基因编辑技术的最新进展,尤其是CRISPR(成簇规律间隔短回文重复序列),为利用微生物群应对复杂的医学挑战开辟了新途径,包括对抗多重耐药病原体和癌症。微生物群通过调节微生物群落、影响病原体存活及对治疗的敏感性,在对抗抗生素耐药性方面发挥着关键作用。本综述探讨了微生物群在代谢调节中的动态作用、其对癌症治疗的贡献,以及AMPs如何在临床前研究结果和临床证据的支持下帮助维持体内平衡并展现出新的抗癌特性。此外,基于CRISPR的微生物群工程有潜力增强宿主与微生物群的相互作用,优化治疗效果。微生物群宏基因组学和蛋白质组学的整合已促成发现具有靶向抗癌作用的新型AMPs。工程益生菌和基于CRISPR的微生物群工程等创新策略为下一代疗法带来了令人兴奋的前景。尽管取得了这些进展,但由于伦理、监管和生态障碍,将基于微生物群的疗法转化为临床应用仍然具有挑战性。本综述强调了基于微生物群的干预措施的变革潜力,强调了个性化医学在最大化治疗效果方面的作用。此外,我们还讨论了关键的研究差距、局限性和未来方向,包括优化AMPs的稳定性、递送和生物利用度,以及克服临床转化中的监管和伦理挑战。