Modulation of the Tumor Microenvironment by Probiotics in Gastrointestinal Cancers: A Comprehensive Review

Gastrointestinal (GI) cancers remain among the leading causes of cancer-related mortality worldwide, with complex etiologies involving genetic, environmental, and microbial factors. Emerging evidence highlights the pivotal role of the gut microbiota and probiotics in modulating the tumor microenvironment (TME), offering novel therapeutic avenues. This comprehensive review explores the molecular mechanisms by which probiotics exert anticancer effects, including apoptosis induction, immune cell activation, suppression of chronic inflammation, and regulation of oncogenic signaling pathways such as PI۳K/AKT, NF-κB, and Wnt/ẞ-catenin. Specific strains such as Lactobacillus rhamnosus, Bifidobacterium bifidum, and Escherichia coli Nissle ۱۹۱۷ demonstrate strain-dependent modulation of immune responses and tumor suppressor gene expression. Additionally, probiotic-derived metabolites like short-chain fatty acids (SCFAs) and bacteriocins contribute to epigenetic reprogramming and tumor inhibition. Despite promising preclinical data, challenges such as host microbiota variability and lack of standardized clinical protocols remain. This review underscores the therapeutic potential of probiotics in GI cancers and advocates for personalized, microbiome-informed interventions.

کلیدواژه ها:

Gastrointestinal cancers ، Tumor microenvironment (TME) ، Probiotics ، Apoptosis induction ، Immune modulation ، Oncogenic signaling pathways