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

Author:

Santonocito Radha1,Paladino Letizia1ORCID,Vitale Alessandra Maria1ORCID,D'Amico Giuseppa1ORCID,Zummo Francesco Paolo1ORCID,Pirrotta Paolo2,Raccosta Samuele3ORCID,Manno Mauro3ORCID,Accomando Salvatore4,D’Arpa Francesco5,Carini Francesco1,Barone Rosario1ORCID,Rappa Francesca1ORCID,Marino Gammazza Antonella1ORCID,Bucchieri Fabio1,Cappello Francesco12ORCID,Caruso Bavisotto Celeste12ORCID

Affiliation:

1. Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy

2. Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy

3. Cell-Tech Hub, Institute of Biophysics, National Research Council of Italy, 90146 Palermo, Italy

4. Department of Health Promotion, Mother and Childcare, Internal Medicine and Medical Specialities “G D‘Alessandro”, PROMISE, University of Palermo, 90127 Palermo, Italy

5. Department of Surgical, Oncological and Stomatological Disciplines, DICHIRONS, University of Palermo, 90127 Palermo, Italy

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®, 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.

Funder

Euro-Mediterranean Institute of Science and Technology

University of Palermo

Publisher

MDPI AG

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