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

HypothesisA 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.MethodSixty 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.ResultThe 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.ConclusionThe 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.

Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome

“…It has been reported that the impact of antibiotics on the gut microbiome can be attributed to its antimicrobial spectrum and the antimicrobial activity in the colon depending on concentrations [ 46 , 47 ]. Previous studies examined the effect of several types of antibiotics on the perturbation of gut microbiota, which may lead to an alteration in colonic mucosal homeostasis and microbial metabolites [ 18 , 27 , 48 , 49 ]. Høverstad et al reported that considerably changed SCFA profiles were observed according to the administration of ampicillin (500 mg four times daily) in the human clinical trial [ 46 ].…”

<p>Methylenetetrahydrofolate Reductase Gene Variants Confer Potential Vulnerability to Autism Spectrum Disorder in a Saudi Community</p>

“…1 Several reports discuss clinical associations, biochemical testing, and therapeutic management of ASD cases in the Saudi population, but very few reports have been published regarding genetic variations in this population. [2][3][4][5] Due to increasing prevalence, ASD brings substantial economic and emotional burdens to affected families and societies. 6 Genetic and environmental factors may play a substantial role in the development of ASD.…”

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“…Disturbances in the gut flora can induce oxidative stress which in turn can increase the neurotoxic effect of the drug and can remarkably affects the brain in rodent models of autism 12 . Several recent studies have shown that dietary factors alter the microbial community resulting in biological changes to the host and overall, dietary changes could explain 57% of the total structural variation in gut microbiota whereas changes in genetics accounted for no more than 12% 18 .…”

“…Ampicillin-induced neurotoxicity has also been described in the literature in very low birth weight neonates 11 . A recent study by El-Ansary 12 has shown ampicillininduced neurotoxicity that might induce autistic traits in animal model of autism.…”