Bifidobacterium bifidum CCFM1163 alleviates cathartic colon by activating the BDNF-TrkB-PLC/IP3 pathway to reconstruct the intestinal nerve and barrier.

Abstract

Introduction: Cathartic colon (CC) is a type of slow-transit constipation caused by a patient's long-term use of irritating laxatives. Probiotics play a crucial role in managing constipation. Objectives: This study aims to identify probiotics that can alleviate CC and explore their specific mechanisms of action. Methods: The CC-model was constructed using senna leaf extract. Bifidobacterium bifidum was applied to the mice for intervention. Relevant marker changes were then examined using ELISA and RT-qPCR. Furthermore, 16S rDNA sequencing was utilized for functional prediction of intestinal microorganisms, while GC-MS analysis was performed to determine the content of short-chain fatty acids (SCFAs) in feces. Results: Senna damages the intestinal nerve and the intestinal barrier while inducing CC. In contrast, Bifidobacterium bifidum CCFM1163 may enhance the brain-derived neurotrophic factor (BDNF) expression in the colon by altering the intestinal microbiota composition (e.g., increasing Lactobacillus and Bacteroides, and decreasing Faecalibaculum) and by elevating SCFA levels (e.g., acetic and isobutyric acid). Subsequently, elevated BDNF expression activates the BDNF-tyrosine kinase receptor B-phospholipase C/inositol trisphosphate (BDNF-TrkB-PLC/IP₃) pathway, which upregulates the gene expression of Uchl1, S100β, and Acta2; repairs the enteric nervous system-interstitial cells of Cajal-smooth muscle cells (ENS-ICC-SMC) network; upregulates the gene expression of Ocln and Tjp1; improves intestinal permeability in CC mice; and modulates the immune response by upregulating Tlr4, downregulating Il1b, and upregulating Il10, ultimately alleviating CC. Conclusion: Bifidobacterium bifidum CCFM1163 was identified as a probiotic that can promote BDNF expression in the colon, activate the BDNF-TrkB-PLC/IP₃ signaling pathway, and effectively alleviate CC.