Beneficial effects of selected food-associated Lactiplantibacillus plantarum on social behaviors, intestinal permeability and gut microbiota in a genetic mouse model of autism spectrum disorders

Several studies demonstrated that neurodevelopmental conditions, such as autism spectrum disorders (ASD), are significantly related to the composition of the gut microbiota whose alterations can influence gastrointestinal (gut dysbiosis and impaired intestinal permeability) and neurobehavioral symptoms. The use of probiotics is emerging as promising alternative approach to ameliorate ASD-associated dysfunctions. This study evaluated whether the administration of probiotic candidate, Lactiplantibacillus plantarum (LP), previously characterized for anti-inflammatory activity, could positively modulate the intestinal microbiota and alleviating ASD-associated intestinal and social impairment in a genetic ASD mouse model. The Neuroligin3 (NLGN3) R451C knock-in (KI) mouse model, showing alterations in the gut microbiome and gastrointestinal dysfunction, was employed as ASD model. Wildtype (WT) and KI mice were fed with selected LP strains (109 CFU/mouse/day) for 5-weeks. Following behavioral testing, mice were sacrificed, and gut and fecal samples were collected. The V3–V4 hypervariable regions of the 16S rRNA gene were targeted for taxonomic profiling of the microbial communities by NGS. Intestinal permeability was assessed by determining the mRNA levels of genes encoding tight junctions’ proteins. Results showed a significant impact of LP on improving social behaviors, restoring intestinal permeability and shaping gut microbiota in KI-LP mice. NGS analysis revealed significant differences in alpha and beta diversity comparing LP-groups leading to a normalized taxa distribution, with decreased Firmicutes/Bacteroidetes ratio in LP-KI mice linked to a relative major increase of some gut-beneficial taxa. LP intake also played a key role in KI mice fostering Akkermansia muciniphila. This study might open new frontiers for the development of dietary therapies for mitigating ASD symptoms; the ultimate translational goal is to develop functional food enriched with specific mixtures of LP strains as targeted and personalized dietary intervention, providing an alternative biotherapeutic strategy in ASD.