Targeting tumor-associated bacteria in digestive system cancers: carcinogenic mechanisms and nano-regulate platform design.

Tumor-associated bacteria (TAB) and their products can reprogram host signaling and metabolism, disrupt tissue homeostasis, and remodel antitumor immunity, collectively creating a cooperative protumor ecosystem. Accumulating evidence indicates that TAB promote the initiation and progression of digestive system malignancies and can also influence therapeutic outcomes. Although conventional bacterial modulation approaches can alter the composition and functions of TAB, their clinical application is hindered by major limitations, including poor in vivo stability, limited targeting specificity, difficulty in penetrating mucosal and tumor barriers, insufficient local persistence, and safety concerns related to dysbiosis. Nanotechnology-based engineering strategies-such as introducing specific ligands, designing biomimetic and stimuli-responsive coatings, improving adhesion and sustained-release performance, and integrating multifunctional modules-can help overcome these constraints, enabling selective elimination of TAB or rebalancing of bacterial communities to enhance anticancer efficacy. This review summarizes the carcinogenic mechanisms of TAB in digestive system cancers and outlines the features and shortcomings of conventional bacterial modulation tools. We further integrate recent advances in nanotechnology-based delivery platforms. Finally, we discuss considerations for translation, emphasizing that multifunctional systems must balance mechanistic synergy with manufacturability and safety, and that future progress may depend on multi-omics-guided patient stratification and modular, biocompatible platform design.