Probiotic Ameliorating Effects of Altered GABA/Glutamate Signaling in a Rodent Model of Autism

Abstract

Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, such as 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. We propose correcting GABA signaling as a therapeutic strategy for ASD. In this study, 40 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 including eight rats. Group I served as the control group and was orally administered phosphate-buffered saline. Groups II and III served as rodent models of ASD and were orally administered a neurotoxic dose of propionic acid (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, a probiotic mixture of ProtexinR, and pure Lactobacillus bulgaricus, respectively, for 3 weeks. Selected variables related to oxidative stress, glutamate excitotoxicity, and gut bacteria were measured in the six groups. Both pure and mixed Lactobacillus and Bifidobacterium were effective in ameliorating glutamate excitotoxicity as an autistic feature developed in the PPA-induced rodent model. Their therapeutic effects mostly involved the correction of oxidative stress, restoration of depleted GABA, and up-regulation of GABA receptor gene expression. Pure Bifidobacterium was the most effective, followed by the mixture of probiotics and finally lactobacillus. In conclusion, Bifidobacteria and lactobacilli can be used independently or in combination as psychobiotics to ameliorate oxidative stress and glutamate excitotoxicity as two confirmed etiological mechanisms through the gut–brain axis.

In Vitro Fermentation of Edible Mushrooms: Effects on Faecal Microbiota Characteristics of Autistic and Neurotypical Children

“…Ahmed et al [ 55 ] revealed that the only significant alteration between the GM of ASD children and that of their healthy siblings was the higher abundance of Bifidobacterium in the siblings’ group, supporting its protective role. Several studies have reported various species of Bifidobacterium as GABA (gamma aminobutyric acid) producers [ 56 , 57 ]. GABA is the main inhibitory neurotransmitter in the brain, the concentrations of which have been found to be diminished in ASD children [ 58 , 59 ].…”

Fecal microbiota transplantation in a child with severe ASD comorbidities of gastrointestinal dysfunctions—a case report

“…Ruminococcus are mucosa-associated bacteria linked with gastrointestinal disease, which have been confirmed that altered in ASD patients ( 25 ). In the mice models, bifidobacteria could play a role in the pathogenesis of ASD by modifying the correction of oxidative stress, and restoration of depleted GABA ( 26 ). We are pleased to be able to find alterations in these flora in the treatment, unfortunately, the abundance changes may be biased because this case involved only one patient.…”

Mechanisms of probiotic modulation of ovarian sex hormone production and metabolism: a review

“…91 The increase in GABA concentrations within the brain of autistic rats after intervention with a single strain and compound strain may be attributed to altered gut microbiota, restoring brain Mg 2+ levels, GABA receptor function, and reducing neurotransmitter glutamate secretion. 92,93 In the negative feedback loop, adipocytes release leptin as an afferent signal. It primarily influences hypothalamic neurons that regulate energy homeostasis and food intake.…”

“…91 The increase in GABA concentrations within the brain of autistic rats after intervention with a single strain and compound strain may be attributed to altered gut microbiota, restoring brain Mg 2+ levels, GABA receptor function, and reducing neurotransmitter glutamate secretion. 92,93…”