Nanovesicular Mediation of the Gut-Brain Axis by Probiotics: Insights into Irritable Bowel Syndrome.
Radha Santonocito, Letizia Paladino, Alessandra Maria Vitale, Giuseppa D'Amico, Francesco Paolo Zummo, Paolo Pirrotta, Samuele Raccosta, Mauro Manno, Salvatore Accomando, Francesco D'Arpa, Francesco Carini, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Fabio Bucchieri, Francesco Cappello, Celeste Caruso Bavisotto
Author Information
Radha Santonocito: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy.
Letizia Paladino: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
Alessandra Maria Vitale: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
Giuseppa D'Amico: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
Francesco Paolo Zummo: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
Paolo Pirrotta: Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy.
Samuele Raccosta: Cell-Tech Hub, Institute of Biophysics, National Research Council of Italy, 90146 Palermo, Italy. ORCID
Mauro Manno: Cell-Tech Hub, Institute of Biophysics, National Research Council of Italy, 90146 Palermo, Italy. ORCID
Salvatore Accomando: Department of Health Promotion, Mother and Childcare, Internal Medicine and Medical Specialities "G D'Alessandro", PROMISE, University of Palermo, 90127 Palermo, Italy.
Francesco D'Arpa: Department of Surgical, Oncological and Stomatological Disciplines, DICHIRONS, University of Palermo, 90127 Palermo, Italy.
Francesco Carini: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy.
Rosario Barone: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
Francesca Rappa: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
Antonella Marino Gammazza: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
Fabio Bucchieri: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy.
Francesco Cappello: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
Celeste Caruso Bavisotto: Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy. ORCID
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 HO, 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 HO-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.
