Live Biotherapeutic Products (LBPs) as Promising Microbiome-Based Medicines for Colorectal Cancer (CRC): Mechanistic Basis, Therapeutic Applications, and Translational Challenges.

Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer worldwide. The gut microbiota profoundly influences this cancer by modulating immune responses and therapeutic efficacy. Recently, live biotherapeutic products (LBPs), comprising live resident microorganisms in the gut, have emerged as promising agents to reprogram host immunity and enhance treatment efficacy in preclinical CRC models. However, translation of these findings to clinical practice remains limited due to heterogeneous study designs, poorly defined mechanisms in human hosts, unresolved manufacturing and safety concerns, and lack of personalized treatment strategies. This review briefly introduces LBPs as a new class of medicines, categorize them as single strains, composite strains, and engineered strains, and details their multifaceted mechanisms against CRC, including direct immunomodulation to enhance anti-tumor activity, production of protective metabolites like short-chain fatty acids (SCFAs), and restoring gut microbiota. Additionally, the synergistic potential of LBPs with conventional chemo- and immunotherapies and current LBPs in clinical trials for CRC are summarized, highlighting their translational progress. We further address the manufacturing, regulatory, and safety barriers constraining clinical adoption and propose strategies for integrating preclinical and clinical evidence to meet patient needs. By consolidating current knowledge of LBPs as an emerging oncology drug class, this review offers a practical framework for advancing LBPs from preclinical promise to clinical practice, supporting the development of personalized medicine.