Lactobacillus johnsonii suppresses colorectal tumorigenesis by enriching the intestinal metabolite to induce tumor cell apoptosis

Lactobacillus johnsonii (LJ) has demonstrated therapeutic potential in various human diseases, but its direct impact on colorectal cancer (CRC) remains insufficiently explored. This study evaluated the prophylactic and therapeutic effects of LJ on colorectal tumors using comprehensive experimental models. Azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse models of CRC and subcutaneous tumor mouse models were employed to assess the effects of LJ. Metagenomic, transcriptomic, and metabolomic analyses identified key metabolites and molecular targets, which were validated in AOM/DSS-induced antibiotic-treated (ABX) mouse models, MC38 xenografts, normal human intestinal epithelial cell lines, and CRC cell lines. LJ treatment significantly enhanced tumor necrosis factor (TNF) signaling pathways, and up-regulated apoptotic gene sets in tumor tissues. Thus, LJ shows considerable potential as a prophylactic and adjunctive therapeutic strategy for CRC management.