A large body of preclinical literature supports the notion of a bidirectional communication system linking the gut and the brain, known as the gut-microbiota-brain axis. Recent evidence indicates that gut microbes can modulate central nervous system (CNS)-driven behaviors in a very powerful way. Thus, the administration of probiotics is emerging as novel potential non-invasive therapeutic alternative to treat a large number of neurological disorders. Specifically, studies have recently found that treatment with the probiotic species Lactobacillus (L.) reuteri reverses the social deficits in several mouse models of Autism. However, the other symptoms associated with the disease, like language and repetitive behaviors are not affected by the treatment with L. reuteri. The aim of this work is to evaluate the effect L. reuteri in combination with Vivinal® GOS, a probiotic strain which has been shown to modulate the gut microbiota and reverse the social deficits, in a genetic model of ASD (Shank3B-/- mice). Briefly, Shank3B-/- mice will be divided into 5 treatment groups: 1: WT control mice, 2: Shank3B-/- mice treated with vehicle; 3: Shank3B-/- mice treated with L. reuteri; 4: Shank3B-/- mice treated with Vivinal® GOS; 5: Shank3B-/- mice treated with both L. reuteri and Vivinal® GOS. We will measure whether the different treatments: a) alter the gut microbiota composition of Shank3B-/- mice by 16S rRNA gene sequence analysis, b) reverse the autism symptoms (social, language and repetitive behaviors) in Shank3B-/- mice and c) alter oxytocin levels in Shank3B-/- mice. The knowledge gained in this study will help to define the basic molecular & cellular mechanisms underlying Autism. Moreover, it could also lead to the development of new probiotic-based non-invasive treatments for patients suffering from Autism and related disorders.
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