Increasing evidence suggests that the gut microbiota plays a key role in the central nervous system (CNS), and alterations of the gut microbiota composition due to environmental factors can contribute to neurodevelopmental disorders. Animal modeling may help to identify drugs that can normalize the altered gut microbiota and thereby ameliorate abnormal brain signaling pathways. The purpose of the present study was to investigate the therapeutic potency of probiotics such as Bifidobacteria and Lactobacilli on glutamate excitotoxicity as a neurotoxic effect induced by clindamycin and propionic acid (PPA) in juvenile hamsters. Fifty young golden Syrian hamsters weighing between 60 and 70 g were enrolled in the study. The hamsters were randomly divided into five groups, each with ten hamsters. The hamsters in the control group only received phosphate-buffered saline orally. The PPA-treated group received a neurotoxic dose of 250 mg PPA/kg body weight (BW)/day for three days. The clindamycin-treated group received 30 mg clindamycin/kg BW as a single orogastric dose on the day the experiment started. The two therapeutic groups received the same doses of PPA and clindamycin followed by 0.2 g probiotic/kg BW for three weeks. Biochemical parameters related to glutamate excitotoxicity were investigated in brain homogenates from each group of hamsters. Additionally, the development of pathogenic bacteria was monitored in stool samples from all groups. The microbiology results of the present study revealed descriptive changes in the fecal microbiota and the appearance of Clostridium species in the hamsters treated with clindamycin and PPA. Additionally, the effectiveness of the probiotic in the restoration of the normal gut microbiota was demonstrated. Moreover, clindamycin and PPA were found to induce a significant depletion of Mg2+ and γ-aminobutyric acid (GABA) and a remarkable increase in the Na+/Mg2+ and glutamate/GABA ratios but non-significant changes in the absolute levels of K+, Na+ and glutamate. The bacteria overgrowth induced by PPA and clindamycin in the present study effectively showed signs of neuronal toxicity. The study indicates that probiotics can be used safely to ameliorate glutamate excitotoxicity mostly through increasing depleted GABA and Mg2+ and decreasing the excitatory neurotransmitter, glutamate.
Keywords: Autism; Clindamycin; Gamma-aminobutyric acid; Glutamate; Glutamate excitotoxicity; Propionic acid.