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 × 109 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.