Abstract
Purpose: To investigate the potency of ampicillin in altering gut flora in the presence of a high-sucrose diet in rat pups, and to determine its effect on selected neurotransmitters and a cytokine as markers of the persistent autistic features repeatedly induced in orally administered propionic acid rat pups..Methods: Twenty-eight young male Wistar albino rats were divided into four equal groups. The first group served as a control. The second group received an oral neurotoxic dose of propionic acid (PPA, 250 mg/kg body weight/day) for 3 days. The third group was treated with ampicillin (50 mg/kg for 3 weeks) with a standard diet. The fourth group was given the same dose of ampicillin with a high-sucrose diet for 10 weeks.Results: The results showed a significant (p < 0.001) decrease in the investigated neurotransmitters in PPA- and ampicillin-treated rat pups (norepinephrine by 32.49 and 14.58 %, dopamine by 31.45 and 20.22 %, serotonin by 35.99 and 29.09 %), as well as a remarkable increase (p < 0.001) in the proinflammatory cytokine, IL-6 (30.07and 6.07 %). The high-sucrose diet also significantly (p < 0.001) enhanced the neurotoxic effect of ampicillin.Conclusion: The observed dietary modulation of the gut microbiota, coupled with the subsequent modulation of brain neurochemistry and inflammation, demonstrates the considerable potential of dietary intervention through the elimination of highly refined sugar as a treatment strategy to prevent and treat autism.Keywords: Neurotoxicity, Ampicillin, Propionic acid, Neurotransmitters, Cytokines, High-sucrose diet
Highlights
INTRODUCTIONAntibiotics are prescribed frequently for infants and children in most pediatric clinics [1].Antibiotic treatment over a long period results in a 10-fold increase of Clostridium spp (propionibacteria) in the gut
Antibiotics are prescribed frequently for infants and children in most pediatric clinics [1].Antibiotic treatment over a long period results in a 10-fold increase of Clostridium spp in the gut. Overgrowth of this species has been reported in autistic patients [2].the induction of persistent autistic features in rodent modelswas achieved by MacFabe et al [3] and El-Ansary et al [4] through propionic acid (PPA) exposure
It is acknowledged that the gut–brain axis and balanced gut microbiota are critically important during brain development and can play a major role in the pathogenesis of autism
Summary
Antibiotics are prescribed frequently for infants and children in most pediatric clinics [1].Antibiotic treatment over a long period results in a 10-fold increase of Clostridium spp (propionibacteria) in the gut Overgrowth of this species has been reported in autistic patients [2].the induction of persistent autistic features in rodent modelswas achieved by MacFabe et al [3] and El-Ansary et al [4] through propionic acid (PPA) exposure. Imbalances in GABAergic/glutamatergic, serotonergic, and dopaminergic neurotransmission together with neuroinflammation were recently reported as the most important signals related to the clinical presentation and severity of autism [7] This information motivated our interest to compare the gut–brain neurotoxic effect of ampicillin to that induced by orally administered PPA as a metabolic end-product of propionibacteria. Receiver operating characteristics curve (ROC) analysis was performed to test the predictive value of the investigated parameters and to measure the toxicity of PPA and ampicillin in intoxicated rats. Multiple regression analysis was conducted using glutamate and IL-6 as two dependent variables against the rest of the variables, which were used as independent or predictor variables
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