Mesenchymal stem cell-derived apoptotic vesicles regulate irritable bowel syndrome in mice via the 5-HT brain-gut axis.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal disorder characterized by abnormal brain-gut interactions. The pathogenic mechanisms of IBS are not fully understood, and current treatments are limited in efficacy. AIMS: This study aims to investigate the potential therapeutic effects of mesenchymal stem cell-derived apoptotic vesicles (apoVs) on IBS in a mouse model, focusing on their impact on the 5-HT brain-gut axis. METHODS: We extracted and characterized apoVs from adipose-derived stem cells (ADSCs, Mesenchymal stem cells derived from adipose) induced to undergo apoptosis. IBS was induced in C57BL/6 mice using a chronic stress model. Mice were treated with apoVs via tail vein injection, and various behavioral, physiological, and biochemical parameters were assessed. RESULTS: IBS patients exhibited increased circulating vesicles in peripheral blood, correlating with brain functional activity. Further animal studies found that apoVs treatment in IBS mice reduced 5-HT levels in the brain and gut, alleviated symptoms such as slowed weight gain and visceral hypersensitivity, and restored intestinal barrier function. Additionally, apoVs improved neuronal activation and mucin secretion in the gut. CONCLUSIONS: Our findings suggest that apoVs act as novel messengers in brain-gut axis interactions, regulating brain-gut homeostasis. This study provides a new therapeutic approach for the treatment of functional gastrointestinal disorders like IBS.