Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 16 1 2024 02 12 68 78 Nafiseh Erfanian Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran Hossein Safarpour Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran Tahmineh Tavakoli Department of Internal Medicine, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran Mohammad Ali Mahdiabadi Department of Internal Medicine, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran Saeed Nasseri Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran Mohammad Hassan Namaei Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran 2023 08 02 2024 02 02 Background and Objectives: Colorectal cancer (CRC) is a prevalent form of cancer worldwide. Recent studies suggest that postbiotics derived from probiotic bacteria have the potential as an adjunct therapy for CRC. This study investigates the anti-cancer effects of Bifidobacterium breve (B. breve) and Lactobacillus rhamnosus (L. rhamnosus) postbiotics on the HT-29 cell line. Materials and Methods: Through MTT and scratch assay, we investigated the anti-proliferation and anti-migration effects of B. breve and L. rhamnosus postbiotics on HT-29 cells. Furthermore, postbiotic-mediated apoptosis was assessed by analyzing the expression of Bax, Bcl-2, and caspase-3. We also investigated the effects of B. breve postbiotics on the expression of three important genes involved in metastasis, including RSPO2, NGF, and MMP7. Consequently, we validated the expression of selected genes in twelve adenocarcinoma tissues. Results: The results demonstrated the significant impact of postbiotics on HT-29 cells, highlighting their ability to induce anti-proliferation, anti-migration, and apoptosis-related effects. Notably, these effects were more pronounced using B. breve postbiotics than L. rhamnosus. Additionally, B. breve postbiotics could inhibit metastasis through upregulation of RSPO2 while downregulating NGF and MMP7 expression in HT-29 cells. Conclusion: Our research suggests that postbiotic metabolites may be effective biological products for the prevention and treatment of cancer. https://ijm.tums.ac.ir/index.php/ijm/article/view/4340 https://ijm.tums.ac.ir/index.php/ijm/article/download/4340/1639