Human clostridia improve visceral hypersensitivity in stressed mice through upregulation of 5-hydroxytryptamine 4

Abstract

Abstract Background Clostridium improves intestinal motility by modulating intestinal 5-hydroxytryptamine (5-HT) levels. However, there are few studies on human clostridia. Aims To evaluate whether human clostridia improves visceral hypersensitivity through the 5-HT4 pathway. Methods An irritable bowel syndrome (IBS) model was established using water avoidance stress (WAS) mice. WAS mice were treated with saline, human clostridial solution (enriched with Clostridium clusters IV ), prucalopride, PCPA, or RS39604 for 1 week, and group differences in body weight, fecal traits, abdominal withdrawal reflex (AWR), and electromyography results were evaluated. Group differences in SLC6A4, TPH1, 5-HT4, PKA, CREB, and pCREB expression in the distal colon and hippocampus and in the number of 5-HT4-expressing intestinal cells were also evaluated. Fecal short-chain fatty acid levels were measured. Results WAS mice showed slower body weight gain, lower fecal water content and Bristol score, and higher visceral sensitivity than the normal group. 5-HT4, PKA, CREB, and pCREB levels and the number of 5-HT4-expressing intestinal cells were lower in the distal colon and hippocampus in WAS mice than in normal mice. After 1 week, human clostridia treatment was superior to other treatments, and the levels of 5-HT4 signaling protein in the intestine and hippocampus and 5-HT4-expressing intestinal cells increased. The TPH1 antagonist PCPA or the 5-HT4 receptor antagonist RS39604 could interfere with the therapeutic effect of the bacterial solution, and human clostridia elevated fecal isovaleric acid levels. Conclusion Human clostridia improved visceral hypersensitivity by upregulating 5-HT4 signaling protein expression in the distal colon and hippocampus, demonstrating its therapeutic potential.