Novel probiotic treatment of autism spectrum disorder associated social behavioral symptoms in two rodent models

Abstract

The prevalence of autism spectrum disorder (ASD) has rapidly increased in the past decades, and several studies report about the escalating use of antibiotics and the consequent disruption of the gastrointestinal microbiome leading to the development of neurobehavioral symptoms resembling to those of ASD. The primary purpose of this study was to investigate whether depletion of the gastrointestinal microbiome via antibiotics treatment could induce ASD-like behavioral symptoms in adulthood. To reliably evaluate that, validated valproic acid (VPA) ASD animal model was introduced. At last, we intended to demonstrate the assessed potential benefits of a probiotic mixture (PM) developed by our research team. Male Wistar rats were used to create antibiotics treated; antibiotics and PM treated; PM treated, VPA treated; VPA and PM treated; and control groups. In all investigations we focused on social behavioral disturbances. Antibiotics-induced microbiome alterations during adulthood triggered severe deficits in social behavior similar to those observed in the VPA model. Furthermore, it is highlighted that our PM proved to attenuate both the antibiotics- and the VPA-generated antisocial behavioral symptoms. The present findings underline potential capacity of our PM to improve social behavioral alterations thus, indicate its promising therapeutic power to attenuate the social-affective disturbances of ASD.

Effects of Probiotics on Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis of Clinical Trials

“…Although animal studies showed that probiotic supplementation improved ASD-like symptoms and social behavior in mice [ 38 , 39 ], in our meta-analysis, the pooled SMD (−0.24, 95% CI: −0.60 to 0.11, p = 0.18) showed that probiotic supplementation did not improve the associated behavioral symptoms in children with ASD, which is consistent with previous findings [ 37 , 40 ]. The pooled SMD in each subgroup by country, scale, and duration of intervention also showed the same results.…”

JUN and PDGFRA as Crucial Candidate Genes for Childhood Autism Spectrum Disorder

“…Specifically, prenatal exposure to maternal immune activation (MIA) is considered a key environmental risk factor for ASD (Han et al, 2021 ; Mirabella et al, 2021 ; Xu et al, 2021 ). Animal models for ASD conducted by prenatal exposure, including prenatal infection, valproic acid, propionic acid, poly (I:C) or lipopolysaccharides exposure, can cause ASD-like behaviors, such as specific impairments in social interaction, communication and repetitive behaviors (Ergaz et al, 2016 ; Mintál et al, 2022 ). The MIA mice model is one of the most frequently studied models of ASD in which a single prenatal exposure to poly (I:C) results in behavioral, neurological, and immunological abnormalities of the offspring (Knuesel et al, 2014 ).…”

A review of probiotics in the treatment of autism spectrum disorders: Perspectives from the gut–brain axis

“…β-endorphin, endogenous opioid peptides, may alter social behavior and result in autistic-like features. A probiotic mixture was shown to attenuate both the antibiotics and VPA-induced autistic behavioral symptoms ( Mintál et al, 2022 ). In the BTBR mouse model of autism, probiotic L. rhamnosus administration decreased behavioral abnormalities in social novelty preference and increased 5-aminovaleric acid and choline levels in serum and the PFC, respectively ( Pochakom et al, 2022 ).…”