FOOD-ASSOCIATED LACTIPLANTIBACILLUS PLANTARUM AS A PROMISING DIETARY INTERVENTION IN THE MICROBIOTA-GUT-BRAIN-AXIS OF A MOUSE MODEL OF AUTISM SPECTRUM DISORDER

Objective: Recently, the use of probiotic is emerging as a promising alternative nutritional approach to address Autism Spectrum Disorder (ASD)-associated neurobehavioral and gastrointestinal dysfunctions, such as gut dysbiosis and impaired intestinal permeability. This study aimed to evaluate whether the administration of probiotic candidates of food-associated Lactiplantibacillus plantarum (LP), with anti-inflammatory activity, could positively modulate the composition of the intestinal microbiota, potentially alleviating ASD-associated intestinal and social symptoms in a genetic ASD mouse model. Methods: The Neuroligin3 (NLGN3) R451C knock-in (KI) mouse model, was employed as monogenic ASD model. Wildtype (WT) and KI mice were fed with selected LP strains for 5-weeks. Following behavioral testing, mice were sacrificed, and gut and fecal samples were collected. Intestinal permeability was assessed by determining the mRNA levels of zonulin-1, claudin 1 and claudin-3. DNA from all fecal samples were subjected to library preparation followed by next-generation sequencing (NGS) of the V3-V4 variable regions of 16S rRNA gene. Results: Results showed a clear impact of LP on improving impaired social behaviors, restoring intestinal permeability and shaping gut microbiota in LP-groups, leading to a normalized taxa distribution. The Firmicutes/Bacteroidetes (F/B) ratio decreased in the LP-treated KI mice thanks to a relative major increase of some gut-beneficial taxa. LP administration also played a key role in KI mice fostering Akkermansia muciniphila. Conclusions: This study confirmed the central role of host- microbe interaction and dietary therapies in mitigating ASD- neurobehavioral and gastrointestinal symptoms, opening new frontiers for the development of targeted and personalized dietary intervention, providing an alternative biotherapeutic strategy in ASD.