121 | Probiotics effect on brain-gut axis mediated by nanovescicles

Alessandro Lo Giudice¹, Giuseppa D’Amico¹, Melania Ionelia Gratie¹, Letizia Paladino², Giusy Vultaggio¹, Adelaide Carista¹, Francesco Cappello¹, Vita Di Stefano³, Celeste Caruso Bavisotto¹ | ¹Institute of Human Anatomy and Histology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Italy; ²Department of Theoretical and Applied Sciences, eCampus University, Novedrate [CO], Italy; ³Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies STEBICEF, University of Palermo, Italy.

Gut dysbiosis is a medical condition caused by the imbalance of the composition of microorganisms that dwell in the gastrointestinal mucosa. It stems from poor diet, stress, infections, and prolonged exposition to antibiotics. Dysbiosis promotes inflammation and contributes to the onset of pathologies such as irritable bowel disease (IBS), leaky gut, and diverticulitis. Moreover, dysbiosis participates in gut-brain axis destabilization, impacting mood, sleep, and stress tolerance [1]. Probiotics are live microorganisms which can support microbiota well-being as they can stimulate immune response, sustain intestinal barrier functional structure, and thwart pathogens. Among their benefits, these microorganisms can contrast dysbiosis and restore normal intestine functioning. Furthermore, the microbiota is a source of various hormones, metabolites, and neurotransmitters that modulate central nervous system (CNS) functions, such as dopamine, γ-aminobutyric acid (GABA), short-chain fatty acids and tryptophan metabolites [2]. In a previous study, we investigated the role of the probiotic mix Acronelle^® (Bromatech S.r.l.) in regulating gut-brain interactions and counteracting dysbiosis [3]. There, we showed that this mix presents a cytoprotective effect towards the intestinal mucosa by decreasing Hsp60 expression and restoring normal levels of tight junction proteins. Also, the mix promoted the kynurenine pathway, a neuroprotective metabolite, by increasing the Tryptophan 2,3-dioxygenase 2 (TDO 2) levels in the pool of circulating nanovesicles and the expression of the serotonin receptor 5-HT2C in the intestinal mucosa model HT29 cell line. Based on these results, our group is currently exploring the effect of another mix, named Psicobrain^® (Bromatech S.r.l.), a probiotic specifically formulated to promote nervous system wellness. Here, we assessed the plasmatic EVs composition of patients suffering from IBS and treated for 60 days with the mix and report a significant increase of another enzyme involved in tryptophan metabolism, Indoleamine 2,3-dioxygenase (IDO), also known for controlling kynurenine pathway initiation in glial cells. In parallel, we are evaluating the effect of the mix on HT29 cells to determine the optimal treatment concentration; subsequently, we will assess its in vitro effects to confirm the stress response and EV composition, and the isolated EVs will then be used to treat glial cells to further investigate their role in gut–brain communication. This second study aims to reinforce the hypothesis established in the previous work and to provide deeper insight into the mechanisms through which probiotics modulate gut–brain signaling.