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.

Afaf El-Ansary,Ramesa Shafi Bhat,Sooad Al-Daihan,Abeer M Al Dbass

doi:10.1186/s13099-015-0054-4

Afaf El-Ansary, Ramesa Shafi Bhat + Show 2 more

Open Access

https://doi.org/10.1186/s13099-015-0054-4

Copy DOI

Journal: Gut Pathogens	Publication Date: Mar 22, 2015
Citations: 57	License type: CC BY 4.0

Affiliation: King Saud University, National Research Centre

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.

Highlights

Human beings and their gut microbiota are in a symbiotic relationship, and a “super organism” that includes both the human organism and microbes has been recently proposed by SommerandBäckhed [1]
The changes observed in the measured parameters reflect the neurotoxic effects of propionic acid (PPA) and ampicillin
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

Summary

Introduction

Human beings and their gut microbiota are in a symbiotic relationship, and a “super organism” that includes both the human organism and microbes has been recently proposed by SommerandBäckhed [1]. Early life events during the initial colonization and microbiota development can determine general and mental health in later life [3,4] Disruptions during these critical periods of dynamic microbiota-host interaction have a great potential to alter brain-gut signaling, affect health throughout life, and increase the risk of neurodevelopmental disorders. It appears that alterations in the gut microbiota during childhood and adolescence could be susceptible to environmental factors, such as the use of antibiotics, stress, poor diet, and infection, which could result in dysbiosis and have a potentially negative impact on general and mental health, leading to the development of brain disorders later in life. Gastrointestinal symptoms have long indicated that gut bacteria might play a role in the pathophysiology of ASD, and various studies have shown that the gut microbiota is altered in ASD, there is little agreement in the literature as to which bacteria might be involved [10,11]

Methods

Results

Conclusion