Synergistic Interactions Between Probiotics and Anticancer Drugs: Mechanisms, Benefits, and Challenges.

Research into the role of probiotics-often referred to as "living supplements"-in cancer therapy is still in its early stages, and uncertainties regarding their effectiveness remain. Relevantly, chemopreventive and therapeutic effects of probiotics have been determined. There is also substantial evidence supporting their potential in cancer treatment such as immunotherapy. Probiotics employ various mechanisms to inhibit cancer initiation and progression. These include colonizing and protecting the gastrointestinal tract (GIT), producing metabolites, inducing apoptosis and autophagy, exerting anti-inflammatory properties, preventing metastasis, enhancing the effectiveness of immune checkpoint inhibitors (ICIs), promoting cancer-specific T cell infiltration, arresting the cell cycle, and exhibiting direct or indirect synergistic effects with anticancer drugs. Additionally, probiotics have been shown to activate tumor suppressor genes and inhibit pro-inflammatory transcription factors. They also increase reactive oxygen species production within cancer cells. Synergistic interactions between probiotics and various anticancer drugs, such as cisplatin, cyclophosphamide, 5-fluorouracil, trastuzumab, nivolumab, ipilimumab, apatinib, gemcitabine, tamoxifen, sorafenib, celecoxib and irinotecan have been observed. The combination of probiotics with anticancer drugs holds promise in overcoming drug resistance, reducing recurrence, minimizing side effects, and lowering treatment costs. In addition, fecal microbiota transplantation (FMT) and prebiotics supplementation has increased cytotoxic T cells within tumors. However, probiotics may leave some adverse effects such as risk of infection and gastrointestinal effects, antagonistic effects with drugs, and different responses among patients. These findings highlight insights for considering specific strains and engineered probiotic applications, preferred doses and timing of treatment, and personalized therapies to enhance the efficacy of cancer therapy. Accordingly, targeted interventions and guidelines establishment needs extensive randomized controlled trials as probiotic-based cancer therapy has not been approved by Food and Drug Administration (FDA).