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INTERNATIONAL CONGRESS OF

CancerGenetics

• Synergistic Effects of Lactobacillus acidophilus-Derived Postbiotics Combined with Chemotherapeutic Agents in Cancer Treatment

• Mansoureh Taghizadeh,¹ Hossein Rastegar,^2,*
  1. Halal Research Center of IRI, Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran
  2. Cosmetic Products Research Center, Iran Food and Drug Administration, Ministry of Health and Medical Education, Tehran, Iran.
  
  
  
• Introduction: The integration of microbial-derived compounds into cancer therapy has emerged as an increasingly promising approach, particularly as limitations of conventional chemotherapeutic drugs—such as cytotoxicity to healthy tissues, drug resistance, and diminished patient tolerance—continue to challenge clinical outcomes. Postbiotics, defined as non-viable microbial products or metabolites that confer health benefits, have gained significant attention due to their stability, safety, and potent bioactive properties. Lactobacillus acidophilus, a widely studied probiotic species, produces diverse postbiotic compounds including organic acids, short-chain fatty acids, bioactive peptides, and exopolysaccharides, many of which exhibit anti-proliferative, pro-apoptotic, and immunomodulatory activities. Recent evidence suggests that when combined with chemotherapeutic drugs, these metabolites may enhance the overall therapeutic response while reducing adverse side effects. However, the extent, mechanisms, and translational relevance of such synergistic interactions remain insufficiently understood. This systematic review aims to synthesize current findings regarding the synergistic anticancer potential of L. acidophilus-derived postbiotics in combination with established chemotherapeutic agents, with a focus on molecular mechanisms, therapeutic enhancement, and implications for future cancer treatment strategies.
• Methods: A comprehensive and systematic literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2000 and 2025. Keywords for database queries included “Lactobacillus acidophilus,” “postbiotics,” “cancer therapy,” “chemotherapeutic synergy,” “combination treatment,” and “apoptosis induction.” Both in vitro and in vivo studies that evaluated the co-administration of L. acidophilus-derived metabolites with chemotherapeutic agents—including doxorubicin, cisplatin, paclitaxel, and 5-fluorouracil—were included. Studies were screened based on predefined inclusion criteria: (1) clear identification of postbiotic components; (2) assessment of cancer cell viability, apoptosis, or tumor progression; (3) evaluation of synergy or interaction with standard chemotherapeutic drugs. Data were extracted regarding experimental model, type of postbiotic, drug combination, dosage, molecular pathways involved, and reported therapeutic outcomes. Findings were qualitatively synthesized due to heterogeneity in study designs and outcome measures.
• Results: Across the reviewed literature, L. acidophilus-derived postbiotics consistently demonstrated the ability to augment the anticancer efficacy of multiple chemotherapeutic drugs. Organic acids—such as lactic acid and acetic acid—were shown to enhance drug uptake by increasing cell membrane permeability and modulating intracellular pH. Bioactive peptides derived from L. acidophilus induced apoptosis through pathways involving caspase activation, mitochondrial membrane depolarization, and suppression of anti-apoptotic genes such as Bcl-2. Exopolysaccharides (EPS) exhibited immunomodulatory effects, enhancing macrophage activation and promoting increased cytotoxic T-cell responses, thereby potentiating the systemic antitumor activity of chemotherapeutic agents. In vitro studies demonstrated significant reductions in cancer cell viability when postbiotics were combined with chemotherapeutic drugs compared to monotherapy. For example, combinations with doxorubicin resulted in enhanced ROS accumulation and accelerated apoptotic signaling. Co-treatment with cisplatin showed greater inhibition of DNA repair pathways, increasing sensitivity of tumor cells to DNA damage. Notably, several studies reported decreased IC50 values for chemotherapeutic drugs when used in combination with postbiotics, indicating improved potency and reduced required dosage. In vivo animal studies further confirmed reduced tumor volume, attenuated metastasis, and improved survival outcomes in combination-treated groups. Importantly, postbiotic supplementation appeared to mitigate chemotherapy-induced toxicity by protecting intestinal epithelial cells, modulating inflammatory cytokines, and stabilizing gut microbiota composition.
• Conclusion: Current evidence strongly supports the synergistic anticancer effects of L. acidophilus-derived postbiotics when used in combination with conventional chemotherapeutic agents. These synergistic interactions occur through multiple mechanisms, including enhanced apoptosis, improved drug uptake, modulation of oxidative stress, immunomodulation, and sensitization of tumor cells to chemotherapeutic damage. Furthermore, the ability of postbiotics to reduce chemotherapy-associated side effects represents a significant therapeutic advantage. Despite promising results, further research is needed to standardize postbiotic formulations, optimize dosage combinations, and conduct clinical trials to validate their safety and efficacy in human patients. Integrating postbiotics into oncology treatment protocols may represent a novel and effective strategy to enhance therapeutic outcomes and improve the quality of life for cancer patients.
• Keywords: Lactobacillus acidophilus , Postbiotics, Chemotherapeutic agents