Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders characterized by impairments in social behavior and communication. Traditional research on the biology of ASDs has focused on the central nervous system (CNS), aiming to identify brain regions, molecular mechanisms, and genetic mutations associated with ASDs. However, an increasingly holistic approach to ASDs demonstrated that there is comorbidity with immune and gastrointestinal (GI) dysfunctions. It is now accepted that there is a bidirectional communication between the gut and the brain, with the microbiota playing an important role in the release of several molecules (such as cytokines, neuropeptides, short chain fatty acids) modulating brain function and behavior. Recent studies support personalized diets rich in probiotics, such as Lactiplantibacillus (Lpb.) plantarum, with proven anti-inflammatory and antioxidant properties. Administrating for 5-weeks the probiotic Lpb. plantarum to the knock-in mouse expressing the R451C mutation in Neuroligin3, a monogenic mouse model of autism, resulted in improvements in social deficits and in the rescue of proper levels of synaptic proteins that were reported to be dysregulated in basal conditions. For testing the behavior, we used the three chambers and the male-female social interaction test and showed an increased interaction with a conspecific WT mouse. Regarding the modulation of the synaptic proteins, we analyzed PSD-95 and Gephyrin levels in the hippocampus and cerebellum brain regions. This study underscores the potential impact of host-microbe interaction in alleviating ASDs-GI symptoms, paving the way for human trials with functional foods containing specific probiotic strains isolated from fermented foods.