Probiotics modulate colorectal cancer in male BALB/c mice via metabolomics and gut microbiota regulation

Globally, colorectal cancer (CRC) continues to be a leading cause of cancer-related death. In male BALB/c mice given a high-fat diet and exposed to pathogenic Escherichia coli and Klebsiella pneumoniae , this study assessed the therapeutic potential of Lactobacillus paracasei . For eight weeks, mice were given an oral supplement of L. paracasei (1 × 10 9 CFU/mouse) every day. Treatment with probiotics significantly decreased aberrant crypt foci and colon tumor lesions (p < 0.05). Mechanistically, L. paracasei rectified cancer-associated metabolic disruptions, especially in lipid and amino acid pathways, and enhanced p53 activity while down regulating VEGF, HIF-1α, and BCL-2. It also restored gut microbial balance. These findings demonstrate pro-apoptotic, immunomodulatory, and anti-inflammatory effects mediated by p53 and HIF-1α/VEGF signaling. Our results give a translational foundation for probiotic-based therapies in human patients and preclinical evidence in favor of probiotics as an adjuvant therapy for colorectal cancer. • Probiotics suppressed oncogenic signaling by reducing levels of VEGF, HIF-1α, and BCL-2. • Gut microbiota composition and immune balance were markedly improved following probiotic supplementation. • GC-MS metabolomics profiling revealed mitigation of cancer-induced disturbances in lipid and amino acid metabolism. • Probiotic treatment exerted anti-inflammatory, pro-apoptotic, and metabolic-restorative effects.