结直肠癌（CRC）是全球第三大癌症。乳酸菌可以调节肠道屏障和肠道微生物群。然而，乳酸菌缓解结直肠癌的机制仍不清楚。本研究旨在探讨植物乳杆菌对结直肠癌的调节作用及其潜在机制。与 ApcMin/ 小鼠的磷酸盐缓冲溶液 (PBS) 治疗相比，CCFM8661 治疗显着改善了 CRC。此外，通过分子生物学技术证明共轭亚油酸（CLA）是CCFM8661改善结直肠癌的关键代谢物。抑制剂干预实验证明过氧化物酶体增殖物激活受体γ（PPAR-γ）是改善结直肠癌的关键受体。此外，补充 CCFM8661 通过产生 CLA 抑制 NF-κB 通路和促炎细胞因子，上调 ZO-1、Claudin-1 和 MUC2，并以 PPAR-γ 依赖性方式促进肿瘤细胞凋亡，从而改善 CRC。宏基因组分析表明，CCFM8661 治疗显着增加了内脏恶臭杆菌，可以通过修复肠道屏障来改善结直肠癌。临床结果显示，CRC患者肠道CLA、丁酸、PPAR-γ、乳酸菌明显下降，且这些指标与CRC呈显着负相关。 CCFM8661 通过 CLA-PPAR-γ 轴改善肠道屏障，从而缓解 CRC。这些结果将促进结直肠癌膳食益生菌补充剂的开发。

Colorectal cancer (CRC) is the third-largest cancer worldwide. Lactobacillus can regulate the intestinal barrier and gut microbiota. However, the mechanisms of Lactobacillus that alleviate CRC remained unknown. This study aimed to explore the regulatory effect of Lactobacillus plantarum on CRC and its potential mechanism. CCFM8661 treatment significantly ameliorated CRC compared with phosphate-buffered solution (PBS) treatment in ApcMin/+ mice. In addition, conjugated linoleic acid (CLA) was proved to be the key metabolite for CCFM8661 in ameliorating CRC by molecular biology techniques. Peroxisome proliferator-activated receptor γ (PPAR-γ) was proved to be the key receptor in ameliorating CRC by inhibitor intervention experiments. Moreover, supplementation with CCFM8661 ameliorated CRC by producing CLA to inhibit NF-κB pathway and pro-inflammatory cytokines, up-regulate ZO-1, Claudin-1, and MUC2, and promote tumor cell apoptosis in a PPAR-γ-dependent manner. Metagenomic analysis showed that CCFM8661 treatment significantly increased Odoribacter splanchnicus, which could ameliorate CRC by repairing the intestinal barrier. Clinical results showed that intestinal CLA, butyric acid, PPAR-γ, and Lactobacillus were significantly decreased in CRC patients, and these indicators were significantly negatively correlated with CRC. CCFM8661 alleviated CRC by ameliorating the intestinal barrier through the CLA-PPAR-γ axis. These results will promote the development of dietary probiotic supplements for CRC.