Postbiotics as Modulators of Apoptotic and Metastatic Pathways in Colorectal Cancer: Insights from HT-۲۹ Cell Responses

Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality worldwide, and its incidence is strongly influenced by diet, lifestyle, chronic inflammation, and the composition of the gut microbiota.[۱–۴] Increasing evidence suggests that microbial dysbiosis contributes to tumor initiation and progression through altered metabolite production, impaired barrier function, and activation of oncogenic signaling pathways such as Wnt/β-catenin, NF-κB, MAPK/ERK, and STAT۳.[۳,۵,۶,۱۴,۱۹] In parallel, interest has grown in microbiota-centered interventions, particularly probiotics, prebiotics, synbiotics, and more recently postbiotics, which are defined as non-viable microbial cells, components, or metabolites that exert health-promoting effects in the host.[۳,۷–۱۰] Postbiotics are attractive because they are stable, safe for immunocompromised patients, and easier to standardize than live probiotics, while still retaining potent immunomodulatory, anti-inflammatory, and anticancer activities.[۷–۱۳,۲۱,۲۶] Experimental and review data indicate that postbiotics can inhibit CRC cell growth, induce apoptosis, modulate the cell cycle, and regulate metastasis-associated genes and pathways, including RSPO۲, NGF, MMP۷, and mitochondrial apoptosis regulators such as Bax, Bcl-۲, and caspase-۳.[۱۰–۱۳,۱۶,۱۷,۲۰] In particular, postbiotics derived from Bifidobacterium breve and Lactobacillus rhamnosus have shown promising effects in HT-۲۹ colorectal cancer cells, where they promote apoptosis and attenuate pro-metastatic gene expression.[۱۰,۲۰] This review summarizes current knowledge on the relationship between the gut microbiota and CRC, defines and contextualizes postbiotics, explores their molecular mechanisms in carcinogenesis with a focus on CRC, and discusses the translational and clinical potential of postbiotics as complementary tools in CRC prevention and management.[۳,۷,۱۱–۱۳,۱۸,۲۶–۲۸]Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality worldwide, and its incidence is strongly influenced by diet, lifestyle, chronic inflammation, and the composition of the gut microbiota.[۱–۴] Increasing evidence suggests that microbial dysbiosis contributes to tumor initiation and progression through altered metabolite production, impaired barrier function, and activation of oncogenic signaling pathways such as Wnt/β-catenin, NF-κB, MAPK/ERK, and STAT۳.[۳,۵,۶,۱۴,۱۹] In parallel, interest has grown in microbiota-centered interventions, particularly probiotics, prebiotics, synbiotics, and more recently postbiotics, which are defined as non-viable microbial cells, components, or metabolites that exert health-promoting effects in the host.[۳,۷–۱۰] Postbiotics are attractive because they are stable, safe for immunocompromised patients, and easier to standardize than live probiotics, while still retaining potent immunomodulatory, anti-inflammatory, and anticancer activities.[۷–۱۳,۲۱,۲۶] Experimental and review data indicate that postbiotics can inhibit CRC cell growth, induce apoptosis, modulate the cell cycle, and regulate metastasis-associated genes and pathways, including RSPO۲, NGF, MMP۷, and mitochondrial apoptosis regulators such as Bax, Bcl-۲, and caspase-۳.[۱۰–۱۳,۱۶,۱۷,۲۰] In particular, postbiotics derived from Bifidobacterium breve and Lactobacillus rhamnosus have shown promising effects in HT-۲۹ colorectal cancer cells, where they promote apoptosis and attenuate pro-metastatic gene expression.[۱۰,۲۰] This review summarizes current knowledge on the relationship between the gut microbiota and CRC, defines and contextualizes postbiotics, explores their molecular mechanisms in carcinogenesis with a focus on CRC, and discusses the translational and clinical potential of postbiotics as complementary tools in CRC prevention and management.[۳,۷,۱۱–۱۳,۱۸,۲۶–۲۸]