Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interactions and communication, restricted interests and repetitive behaviors. Several studies report a high prevalence of gastrointestinal (GI) symptoms in autistic individuals. Cumulative evidence reveals that the gut microbiota and its metabolites (especially short-chain fatty acids, SCFAs) play an important role in GI disorders and the pathogenesis of ASD. However, the composition of the gut microbiota and its association with fecal SCFAs and GI symptoms of autistic children remain largely unknown. In the present study, we sequenced the bacterial 16S rRNA gene, detected fecal SCFAs, assessed GI symptoms and analyzed the relationship between the gut microbiome and fecal SCFAs in autistic and neurotypical individuals. The results showed that the compositions of the gut microbiota and SCFAs were altered in ASD individuals. We found lower levels of fecal acetic acid and butyrate and a higher level of fecal valeric acid in ASD subjects. We identified decreased abundances of key butyrate-producing taxa (Ruminococcaceae, Eubacterium, Lachnospiraceae and Erysipelotrichaceae) and an increased abundance of valeric acid associated bacteria (Acidobacteria) among autistic individuals. Constipation was the only GI disorder in ASD children in the present study. We also found enriched Fusobacterium, Barnesiella, Coprobacter and valeric acid-associated bacteria (Actinomycetaceae) and reduced butyrate-producing taxa in constipated autistic subjects. It is suggested that the gut microbiota contributes to fecal SCFAs and constipation in autism. Modulating the gut microbiota, especially butyrate-producing bacteria, could be a promising strategy in the search for alternatives for the treatment of autism spectrum disorder.
Objective To systematically evaluate evidence for the use of interventions based on appied behavior analysis (ABA) to manage various symptoms of children with autism spectrum disorder (ASD).Methods Sensitivity analyses were conducted by removing any outlying studies and subgroup analyses were performed to compare the effectiveness of ABA and early start denver model (ESDM), picture exchange communication systems (PECS) and discrete trial training (DTT).Results 14 randomized control trials of 555 participants were included in this meta-analysis. The overall standardized mean difference was d=-0.36 (95% CI -1.31, 0.58; Z=0.75, p=0.45) for autism general symptoms, d=0.11 (95% CI -0.31, 0.54; Z=0.52, p=0.60) for socialization, d=0.30 (95% CI -0.02, 0.61; Z=1.84, p=0.07) for communication and d=-3.52 (95% CI -6.31, -0.72; Z=2.47, p=0.01) for expressive language, d=-0.04 (95% CI -0.44, 0.36; Z=0.20, p=0.84) for receptive language. Those results suggested outcomes of socialization, communication and expressive language may be promising targets for ABA-based interventions involving children with ASD. However, significant effects for the outcomes of autism general symptoms, receptive language, adaptive behavior, daily living skills, IQ, verbal IQ, nenverbal IQ, restricted and repetitive behavior, motor and cognition were not observed.Conclusion The small number of studies included in the present study limited the ability to make inferences when comparing ABA, ESDM, PECS and DTT interventions for children with ASD.
Context: Morphine is an alkaloid isolated from the poppy plants. The addiction of morphine is a very serious social issue. Some long non-coding RNAs (lncRNAs) have been proposed to engage in drug addiction. Objective: Whether lncRNA maternally expressed gene 3 (MEG3) attended to morphine-mediated autophagy of mouse hippocampal neuronal HT22 cells was probed. Materials and methods: HT22 cells were subjected to 10 µM morphine for 24 h. Cell autophagy was assessed by measuring LC3-II/LC3-I and Beclin-1 expression. qRT-PCR was carried out to measure MEG3 expression. SiRNA oligoribonucleotides targeting MEG3 (si-MEG3) was transfected to silence MEG3. The orexin1 receptor (OX1R), c-fos, p/t-ERK and p/t-PKC expressions were tested by western blotting. SCH772984 was used as an inhibitor of ERK pathway. Results: Morphine elevated OX1R (2.92 times), c-fos (2.06 times), p/t-ERK (2.04 times) and p/t-PKC (2.4 times), Beclin-1 (3.2 times) and LC3-II/LC3-I (3.96 times) expression in HT22 cells. Moreover, followed by morphine exposure, the MEG3 expression was also elevated in HT22 cells (3.03 times). The silence of MEG3 lowered the Beclin-1 (1.85 times), LC3-II/LC3-I (2.12 times), c-fos (1.39 times) and p/t-ERK (1.44 times) expressions in morphine-treated HT22 cells. Inhibitor of ERK pathway SCH772984 further promoted the influence of MEG3 silence on morphine-caused Beclin-1 (1.97 times) and LC3-II/LC3-I (1.92 times) expressions decreases. Conclusions: Up-regulation of MEG3 attended to the morphine-caused autophagy of HT22 cells might be through elevating c-fos expression and promoting ERK pathway activation. More experiments are also needed in the future to analyse the influence of other lncRNAs in drug addiction.
Autism is a common neurodevelopmental disorder that severely affects patients’ quality of life. We aimed to investigate whether acupuncture at Zusanli (ST36) could alleviate the behavior disorder of autistic rats by inhibiting thioredoxin-interacting protein (TXNIP)-mediated activation of NLRP3. An autism model was induced by intraperitoneal injection of pregnant rats with valproic acid (VPA). The pups’ behaviors were analyzed using hot plate, open field, Morris water maze, and 3-chamber social interaction tests. Nissl staining was used to visualize neurons in prefrontal cortex. Levels of TXNIP, NLRP3, interleukin (IL)-1β, and caspase were determined by Western blot or quantitative real-time PCR. After ST36 acupuncture, pain sensitivity, autonomous activity, sociability index, sociability preference index, and learning and memory were improved in the autism model rats. Levels of TXNIP, NLRP3, IL-1β, and caspase 1 were decreased after acupuncture. Interference with TXNIP alleviated the behavior disorders and inhibited NLRP3, caspase 1, and IL-1β levels. In summary, ST36 acupuncture reduced TXNIP expression, inhibited the activation of the NLRP3 inflammasome, and alleviated the behavior disorder related to the prefrontal cortex of the autistic rats. These results point to a potential mechanism for acupuncture-induced improvement of autistic behavioral disorders.
Autism spectrum disorders (ASD) are a class of neurodevelopmental conditions with a large societal impact. Despite existing evidence suggesting a link between ASD pathogenesis and gut–brain axis dysregulation, there is no systematic review of the treatment of probiotics on ASD and its associated gastrointestinal abnormalities based on the gut–brain axis. Therefore, we performed an analysis for ASD based on preclinical and clinical research to give a comprehensive synthesis of published evidence of a potential mechanism for ASD. On the one hand, this review aims to elucidate the link between gastrointestinal abnormalities and ASD. Accordingly, we discuss gut microbiota dysbiosis regarding gut–brain axis dysfunction. On the other hand, this review suggests that probiotic administration to regulate the gut–brain axis might improve gastrointestinal symptoms, restore ASD-related behavioral symptoms, restore gut microbiota composition, reduce inflammation, and restore intestinal barrier function in human and animal models. This review suggests that targeting the microbiota through agents such as probiotics may represent an approach for treating subsets of individuals with ASD.
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