Abstract
The gut microbiome has emerged as a critical determinant of cancer immunotherapy efficacy, influencing treatment response, resistance, and immune-related toxicity through complex interactions with host immune pathways. Recent evidence highlights the roles of beneficial microorganisms, including Akkermansia muciniphila, Bifidobacterium spp., and Faecalibacterium prausnitzii, as well as microbial metabolites such as short-chain fatty acids, secondary bile acids, and tryptophan derivatives, in regulating anti-tumor immunity. However, conventional cell culture systems and animal models often fail to accurately replicate the dynamic interactions among microbial communities, host tissues, immune cells, and tumors. This review examines how mechanical engineering innovations are transforming microbiome–cancer research through the development of microfluidic devices, gut-on-a-chip systems, tumor-on-a-chip platforms, three-dimensional bioprinting technologies, and advanced biosensors. These technologies enable precise control of physiological conditions, real-time monitoring of microbial and immune responses, and recreation of clinically relevant tumor microenvironments. The review further discusses their applications in modeling host–microbe communication, predicting immunotherapy responses, evaluating drug resistance, and facilitating personalized therapeutic screening. Major translational challenges, including standardization, manufacturing scalability, regulatory approval, and clinical validation, are critically assessed. The current evidence indicates that engineering-driven platforms provide powerful tools for decoding microbiome-mediated regulation of cancer immunotherapy and offer a foundation for next-generation precision oncology. Future integration of artificial intelligence, microbiome engineering, nanotechnology, and patient-specific organ-on-a-chip systems may enable highly personalized immunotherapeutic strategies and improve clinical outcomes