Department of General Practice, People's Hospital of Longhua, Shenzhen 518109, China.
Department of Gastroenterology, People's Hospital of Longhua, Shenzhen 518109, China.
Molecules. 2022 Jul 27;27(15):4799. doi: 10.3390/molecules27154799.
The human gut is inhabited by hundreds of billions of commensal microbiota that collectively produce thousands of small molecules and metabolites with local and systemic effects on the physiology of the host. Much evidence from preclinical to clinical studies has gradually confirmed that the gut microbiota can regulate anti-tumor immunity and affect the efficacy of cancer immune checkpoint inhibitors (ICIs) therapy. In particular, one of the main modes of gut microbiota regulating anti-tumor immunity is through metabolites, which are small molecules that can be transported in the body and act on local and systemic anti-tumor immune responses to promote ICIs immunotherapy efficacy. We discuss the functions of microbial metabolites in humans, focusing on the effects and mechanisms of microbial metabolites on immunotherapy, and analyze their potential applications as immune adjuvants and therapeutic targets to regulate immunity and enhance ICIs. In summary, this review provides the basis for the rational design of microbiota and microbial metabolite-based strategies of enhancing ICIs.
人体肠道中栖息着数以千亿计的共生微生物菌群，它们共同产生数千种小分子和代谢物，对宿主的生理机能具有局部和全身影响。从临床前研究到临床研究的大量证据逐渐证实，肠道微生物群可以调节抗肿瘤免疫，并影响癌症免疫检查点抑制剂（ICI）治疗的疗效。特别是，肠道微生物群调节抗肿瘤免疫的主要方式之一是通过代谢物，代谢物是可以在体内运输并作用于局部和全身抗肿瘤免疫反应的小分子，以促进 ICI 免疫治疗的疗效。我们讨论了微生物代谢物在人类中的功能，重点分析了微生物代谢物对免疫治疗的影响和作用机制，并分析了它们作为免疫佐剂和治疗靶点的潜在应用，以调节免疫并增强 ICI。总之，本综述为合理设计基于微生物组和微生物代谢物的增强 ICI 策略提供了依据。
