Gut-brain axis: effects of probiotics on behavior and function

Fermented food microbes are gaining increasing attention for their health-promoting potential and for being genetically related to human probiotic bacteria. Among them, Lactiplantibacillus (Lpb.) plantarum represents a versatile and robust dominant specie in fermented foods, safe for humans and with anti-inflammatory and antioxidant properties, on top of its ability to modulate compromised gastrointestinal microbiota. The gut microbiota has been shown to modulate brain function and behavior. The endocannabinoid system (ECS) is one of the major modulators in the microbiota–gut–brain signaling pathways and is linked to the inhibitory GABAergic neurotransmitter system in the brain. ASDs are complex syndromes characterized by behavioral impairments in social interaction and by altered neurotransmission with an imbalance between excitatory/inhibitory pathways. We have tested the effect of Lpb. plantarum supplementation to ameliorate endophenotypes associated with ASDs in the Neuroligin3 (NLGN3) R451C mouse, a monogenic model of autism presenting highly reduced levels of post-synaptic NLGN3, social deficits, altered synaptic transmission and gastro-intestinal dysfunction. After a 5-weeks long treatment with Lpb. Plantarum, we investigated the rescue of impaired social deficits by several behavioral tests, such as three chamber and the male-female social interaction test, and found an increase in time R451C mice interacted with a co-specific WT mouse. We also found a modulation of the ECS, after the treatment. Overall, our findings point toward an effective cross-talk between functional microorganisms and ECS in ameliorating the phenotype of a mouse model of ASD. These encouraging results underline a potential implication of the host-microbe interaction in terms of alleviation of ASD-GI symptoms, opening the way to human clinical trials in order to develop functional foods that can vehicle specific probiotic strains directly isolated from fermented foods.