Gut Microbiota-Bile Acid Crosstalk in Diarrhea-Irritable Bowel Syndrome

Figure 2

Summary of the possible signaling pathway between gut microbiota-bile acids axis and IBS-D. The metabolic disorder of the gut microbiota-bile acid axis could lead to the higher secretion levels of secondary BAs, which activate a series of signaling pathways in the intestinal epithelium, resulting in VH, damage of intestinal mucosal barrier function, increased intestinal motility, and increased intestinal bile acid excretion, thus promoting the occurrence of IBS-D. On the one hand, the reduced expression of FXR can not only upregulate the NGF/TRPV1 signaling pathway to cause VH but also downregulate FGF19/15 that can regulate the JNK1/2 and ERK1/2 signaling pathway to make an inhibition on intestinal barrier function and promote autophagy. On the other hand, the increased secondary BAs can activate TGR5 on EC cells to up-regulate the expression of 5–HT and CGRP, causing increased colonic motility. At the same time, 5-HT could upregulate the release of 5-HT3R to cause VH and transmit stimulus to the spinal cord, the process of which may be involved in the brain-gut interaction. Abbreviations: BAs: bile acids; FXR: farnesoid X receptor; NGF: nerve growth factor; TRPV1: transient receptor potential vanilloid 1; VH: visceral hypersensitivity; FGF19/15: fibroblast growth factor (FGF) 19/15; JNK: c-Jun N-terminal kinase; ERK: extracellular signal-regulated kinase; TJ: tight junction; CYP7A1: cholesterol 7α-hydroxylase; SHP: small heterodimer partner; TGR5: G-protein-coupled bile acid receptor 1; 5-HT: 5-hydroxytryptamine; 5-HT3R: 5-hydroxytryptamine 3 receptor; CGRP: calcitonin gene-related peptide; EC: enterochromaffin; SCFA: short-chain fatty acids; ENS: enteric nervous system; CNS: central nervous system; VDR: vitamin D receptor.