High CLA-producing Lactiplantibacillus plantarum MNN1 alleviates irritable bowel syndrome through activation of intestinal PPARα signaling pathway.

Irritable bowel syndrome (IBS) is a common gut-brain axis disorder characterized by visceral hypersensitivity, abdominal pain, and anxiety. Although probiotics have emerged as a promising strategy for IBS management, the specific metabolite-driven mechanisms and their role in gut-brain axis modulation remain largely unclear. In this study, 18 Lactiplantibacillus plantarum strains were screened for conjugated linoleic acid (CLA) production, and strain MNN1 was identified as a high-CLA producer, with a yield of 426 μmol/L, approximately threefold higher than that of the reference strain WCFS1. Then, we evaluated the effects of MNN1 in a mouse IBS model. Oral administration of MNN1 alleviated IBS-like symptoms, including visceral hypersensitivity, elevated fecal moisture, and colon shortening. It also ameliorated anxiety-like behaviors, decreased serum corticosterone levels (indicating suppression of hypothalamic-pituitary-adrenal axis overactivation) and restored hippocampal neuronal integrity. Histological and molecular analyses of colonic tissues demonstrated that MNN1 attenuated mucosal inflammation, increased goblet cell numbers and enhanced epithelial barrier integrity through upregulation of MUC2, ZO-1, and Occludin. Transcriptomic profiling of colon tissue revealed that MNN1 enriched the PPAR signaling pathway (Rich Ratio = 2.0) and downregulated genes associated with visceral hypersensitivity. MNN1 activated colonic PPARα, promoting intestinal stem cell markers (Lgr5, Wnt3) and increasing Ki67+ and SOX9+ cells, indicating enhanced epithelial repair. Metagenomic sequencing confirmed that MNN1 reshaped gut microbiota composition by enriching beneficial taxa and CLA synthesis pathways (e.g., the abundance of K10254, a key gene in CLA synthesis, increased by 2.57-fold). Consequently, colonic CLA levels were elevated, which further reinforced PPARα-mediated anti-inflammatory and barrier-enhancing responses. In conclusion, these findings demonstrate that MNN1 alleviates gut-brain axis dysfunction in IBS through microbiota-dependent CLA production and activation of PPARα signaling, providing a probiotic intervention strategy for IBS.