Nanovesicular Mediation of the Gut-Brain Axis by Probiotics: Insights into Irritable Bowel Syndrome

Simple Summary In this study, we studied the potential health benefits of probiotic supplements in individuals with chronic diarrhea. Dysbiosis, resulting from factors like poor diet or stress, can lead to various systemic diseases. Probiotics are known for stabilizing gut microbiota and alleviating gastrointestinal issues, such as irritable bowel syndrome (IBS). We focused on the tryptophan pathway's role in regulating serotonin levels and its impact on host physiology and behavior. Nanovesicles isolated from subjects' plasma before and after 60 days of probiotics consumption showed enhanced levels of Tryptophan 2,3-dioxygenase 2 (TDO 2), suggesting a potential role in the gut-brain axis. In vitro experiments demonstrated the probiotics' cytoprotective effect against H2O2-induced stress, reducing heat shock protein 60 kDa levels and preserving intestinal integrity. Moreover, the probiotics increased TDO 2 and serotonin receptor expression. These results provide evidence for the role of nanovesicles in mediating the gut-brain axis and offer insights into potential therapeutic avenues for neurological disorders.Abstract Background: Dysbiosis, influenced by poor diet or stress, is associated with various systemic diseases. Probiotic supplements are recognized for stabilizing gut microbiota and alleviating gastrointestinal issues, like irritable bowel syndrome (IBS). This study focused on the tryptophan pathways, which are important for the regulation of serotonin levels, and on host physiology and behavior regulation. Methods: Nanovesicles were isolated from the plasma of subjects with chronic diarrhea, both before and after 60 days of consuming a probiotic mix (Acronelle (R), Bromatech S.r.l., Milan, Italy). These nanovesicles were assessed for the presence of Tryptophan 2,3-dioxygenase 2 (TDO 2). Furthermore, the probiotics mix, in combination with H2O2, was used to treat HT29 cells to explore its cytoprotective and anti-stress effect. Results: In vivo, levels of TDO 2 in nanovesicles were enhanced in the blood after probiotic treatment, suggesting a role in the gut-brain axis. In the in vitro model, a typical H2O2-induced stress effect occurred, which the probiotics mix was able to recover, showing a cytoprotective effect. The probiotics mix treatment significantly reduced the heat shock protein 60 kDa levels and was able to preserve intestinal integrity and barrier function by restoring the expression and redistribution of tight junction proteins. Moreover, the probiotics mix increased the expression of TDO 2 and serotonin receptors. Conclusions: This study provides evidence for the gut-brain axis mediation by nanovesicles, influencing central nervous system function.