Probiotic ameliorating effects of altered GABA/glutamate signaling in a rodent model of autism

Background: Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and nonverbal communication, social skills, and cognition. Excitatory/inhibitory (E/I) imbalances have been recorded as an etiological mechanism of ASD. Furthermore, GABA, the main inhibitory neurotransmitter in adult life is known to be much lower in both patients and rodent models of ASD. Methods: In the present study, forty young male western Albino rats, 3–4 weeks in age, weighing about 60–70 g were used. The animals were randomly assigned into six experimental groups; each of them included eight rats. Group (I) serves as control orally given phosphate-buffered saline. Groups (II, III) serve as a rodent model of ASD, orally administered a neurotoxic dose of PPA. The rats in the three therapeutic groups (IV, V, and IV) received the same doses of PPA followed by 0.2 g/kg body weight of pure Bifidobacterium infantis, the probiotic mixture of (ProtexinR), and pure Lactobacillus bulgaricus respectively for three weeks. Selected variables related to oxidative stress, glutamate excitotoxicity, and gut bacteria were measured in the six studied groups. Results: Both pure or mixed Lactobacillus and Bifidobacterium were effective in ameliorating glutamate excitotoxicity as an autistic feature developed in the PPA-induced rodent model. Their therapeutic effects were mostly through, the correction of oxidative stress, restoring the depleted GABA neurotransmitter, and up-regulating the gene expression of GABA receptors. Pure Bifidobacterium was the most effective followed by the mixture of probiotics, and finally lactobacillus. Conclusion: Bifidobacteria and lactobacilli could be used either independently or in combination as psycho-biotics to ameliorate oxidative stress and glutamate excitotoxicity as two confirmed etiological mechanisms through the gut-brain axis.