Anticancer Activity of Lactiplantibacillus plantarum subsp. plantarum IIA-1A5-Fermented Milk on Chemically Induced-Colorectal Cancer of BALB/c Mice

Colorectal cancer (CRC) remains a significant global health challenge, with current treatment options often limited by toxicity, resistance, and adverse effects. Probiotics, particularly lactic acid bacteria (LAB), offer promising alternatives through bioactive metabolites with anticancer and immunomodulatory properties. The indigenous Indonesian strain Lactiplantibacillus plantarum subsp. plantarum IIA-1A5 exhibits unique metabolic profiles and has demonstrated in vitro anticancer potential. This study evaluated the anticancer effects of L. plantarum IIA-1A5–fermented milk in an AOM and DSS-induced murine model, focusing on aberrant crypt foci (ACF), tumor cell density, malondialdehyde (MDA), cortisol levels, gut microbiota composition, and NF-κB expression. The curative intervention group (P5) exhibited the most pronounced effects, including significant reductions in ACF, tumor cell density, MDA levels, and serum cortisol, reflecting decreased oxidative and physiological stress. Importantly, NF-κB expression was markedly suppressed, indicating attenuation of pro-inflammatory signaling pathways pivotal to CRC progression. Favorable modulation of gut microbiota was also observed, particularly through suppression of Escherichia coli. Compared to 5-fluorouracil (5-FU), L. plantarum IIA-1A5 demonstrated comparable efficacy in mitigating oxidative stress, inflammation, and microbial dysbiosis. These findings highlight the potential of L. plantarum IIA-1A5 as a functional probiotic with both preventive and therapeutic applications in colorectal cancer management. Further mechanistic and clinical studies are warranted to validate these effects and assess their translational relevance in humans.