<i>Lactobacillus plantarum</i> Ameliorates Colorectal Cancer by Ameliorating the Intestinal Barrier through the CLA-PPAR-γ Axis

Abstract

Colorectal cancer (CRC) is the third-largest cancer worldwide. <i>Lactobacillus</i> can regulate the intestinal barrier and gut microbiota. However, the mechanisms of <i>Lactobacillus</i> that alleviate CRC remained unknown. This study aimed to explore the regulatory effect of <i>Lactobacillus plantarum</i> on CRC and its potential mechanism. CCFM8661 treatment significantly ameliorated CRC compared with phosphate-buffered solution (PBS) treatment in Apc^Min/+ 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 <i>Odoribacter splanchnicus</i>, which could ameliorate CRC by repairing the intestinal barrier. Clinical results showed that intestinal CLA, butyric acid, PPAR-γ, and <i>Lactobacillus</i> 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.