Nanovesicles in the Gut–brain Axis: Insights From Probiotic Supplementation in Irritable Bowel Syndrome

Dysbiosis, often caused by poor diet or chronic stress, disrupts gut balance and is linked to various intestinal and systemic diseases1. Probiotics help restore microbiota stability and relieve irritable bowel syndrome (IBS) symptoms2, including effects on the central nervous system (CNS). This study investigates the influence of probiotics on bowel-derived nanovesicles composition, particularly for what concerns the possibility of influencing the so-called “gut–brain axis” by acting on the tryptophan metabolic pathway, since the latter is pivotal in serotonin regulation and in modulating host neurophysiology and behavior3. Plasma-derived nanovesicles were isolated from individuals affected by IBS with diarrhoea, both before and after a 60-day supplementation with a multi-strain probiotic formulation. The levels of tryptophan 2,3-dioxygenase 2 (TDO2) within these vesicles were analyzed, revealing its increase following probiotic supplementation. To further explore the mechanistic effects of probiotics, HT29 intestinal epithelial cells were treated with the probiotic mix in the presence (or not) of hydrogen peroxide (H₂O₂) for inducing oxidative stress. The supplementation with the same probiotic mix used in the in vivo study exhibited a marked cytoprotective effect by attenuating the H₂O₂-induced stress response: e.g., probiotic exposure led to a significant reduction of HSP60 protein levels and to a restoration of tight junction proteins, putatively contributing to preserving/remodeling the epithelial barrier integrity. Additionally, an upregulation of both TDO2 and serotonin receptor levels was observed in these cells. To confirm our in vivo data, we isolated nanovesicles from HT29 cells treated with the probiotics mix and, remarkably, TDO2 levels were higher in nanovesicles from treated cells compared to the controls4. Our findings suggest that probiotic-induced nanovesicles may influence CNS function through the gut–brain axis and help maintain gut homeostasis under stress.