The neurotoxic effects of ampicillin-associated gut bacterial imbalances compared to those of orally administered propionic acid in the etiology of persistent autistic features in rat pups: Effects of various dietary regimens

Abstract

Hypothesis: A healthy gut with normal intestinal microflora is completely disrupted by oral antibiotics. The byproducts of harmful gut bacteria can interfere with brain development and may contribute to autism. Strategies to improve the gut microflora profile through dietary modification may help to alleviate gut disorders in autistic patients. Method: Sixty young male western albino rats were divided into six equal groups. The first group served as the control; the second group was given an oral neurotoxic dose of propionic (PPA) (250 mg/kg body weight/day) for three days. The third group received an orogastric dose of ampicillin (50 mg/kg for three weeks) with a standard diet. Groups 4, 5 and 6 were given an orogastric dose of ampicillin and fed high-carbohydrate, high-protein and high-lipid diets, respectively, for 10 weeks. Biochemical parameters related to oxidative stress were investigated in brain homogenates from each group. Result: The microbiology results revealed descriptive changes in the fecal microbiota of rats treated with ampicillin either alone or with the three dietary regimens. The results of PPA acid and ampicillin treatment showed significant increases in lipid peroxidation and catalase with decreases in glutathione and potassium compared with levels in the control group. A protein-rich diet was effective at restoring the glutathione level, while the carbohydrate-rich diet recovered lipid peroxidation and catalase activity. In addition, the three dietary regimens significantly increase the potassium level in the brain tissue of the test animals. Lactate dehydrogenase was remarkably elevated in all groups relative to the control. No outstanding effects were observed in glutathione S-transferase and creatine kinase. Conclusion: The changes observed in the measured parameters reflect the neurotoxic effects of PPA and ampicillin. Lipid peroxide and catalase activity and the levels of glutathione and potassium are satisfactory biomarkers of PPA and ampicillin neurotoxicity. Based on the effects of the three dietary regimens, a balanced diet can protect against PPA or ampicillin-induced neurotoxicity that might induce autistic traits. These outcomes will help efforts directed at controlling the prevalence of autism, a disorder that has recently been associated with PPA neurotoxicity.