AR495 improves colonic transport hyperactivity in irritable bowel syndrome through tryptophan metabolism.

AR495 is a widely used probiotic for the treatment of various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of AR495 in alleviating IBS remain unclear. Abnormal intestinal tryptophan metabolism can cause disordered immune responses, gastrointestinal peristalsis, digestion and sensation, which is closely related to IBS pathogenesis. The aim of this study is to explore the effects and mechanisms of AR495 in regulating tryptophan metabolism. Primarily, tryptophan and its related metabolites in patients with IBS and healthy people were analyzed, and an IBS rat model of acetic acid enema plus restraint stress was established to explore the alleviation pathway of AR495 in tryptophan metabolism. It was found that the 5-HT pathway was significantly changed, and the 5-HTP and 5-HT metabolites were significantly increased in the feces of patients with IBS, which were consistent with the results obtained for the IBS rat model. Maladjusted 5-HT could increase intestinal peristalsis and lead to an increase in the fecal water content and shapeless stool in rats. On the contrary, these two metabolites could be restored to normal levels intragastric administration of AR495. Further study of the metabolic pathway showed that AR495 could effectively reduce the abundance of 5-HT by inhibiting the expression of enterochromaffin cells rather than promoting its decomposition. In addition, the results showed that AR495 did not affect the expression of SERT. To sum up, AR495 could restore the normal levels of 5-HT by inhibiting the abnormal proliferation of enterochromaffin cells and the excessive activation of TPH1 to inhibit the intestinal peristalsis in IBS. These findings provide insights for the use of probiotics in the treatment of IBS and other diarrheal diseases.