The effects of probiotics and prebiotics on gastrointestinal and behavioural symptoms in autism spectrum disorder

2021 ◽  
Vol 16 ◽  
Author(s):  
José Guevara-Gonzaléz ◽  
José Guevara-Campos ◽  
Lucía González ◽  
Omar Cauli
Keyword(s):  
Gut Microbiota ◽  
Autism Spectrum ◽  
Current Evidence ◽  
Unknown Etiology ◽  
Behavioural Symptoms ◽  
Beneficial Effects ◽  
Behavioral Abnormalities ◽  
Spectrum Disorders ◽  
Different Strains ◽  
The Brain

Background: Autism spectrum disorders (ASDs) are a group of prevalent neuropsychiatric disorders. They present a complex and unknown etiology, which in most cases includes significant peripheral alterations outside the brain such as in the composition of gut microbiota. Because the gut microbiota is involved in modulating the gut–brain axis, several studies have suggested that the microbiome in the gut can modify metabolites which are able to cross the blood–brain barrier and modulate brain function. Methods: we reviewed the current evidence regarding microbiota alterations in patients with ASD and the effects of the administration of probiotics and prebiotics in these patients, both in terms of gastrointestinal and behavioural symptoms. Results: Administration of a probiotic formulation containing different strains of Lactobacillus (L. acidophilus, L. rhamnosus, and others) and Bifidobacteria had beneficial effects upon these aforementioned symptoms and their use is recommended in a subgroup of ASD patients that present gastrointestinal disturbances, Nonetheless, the types of gastrointestinal disturbances that most benefit from such interventions remains to be elucidated in order to personalize the medical approaches. Conclusion: Recent clinical studies have shown that probiotic treatments can regulate the gut microbiota and may result in improvements in some behavioral abnormalities associated with ASD. Trials using prebiotic fibers or synbiotics preparations are still lacking and necessary in order to deep in such therapeutic strategies in ASD with comorbid gastrointestinal disrturbances

scholarly journals Autism Spectrum Disorders and the Gut Microbiota

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 521 ◽  
Author(s):  
Antonella Fattorusso ◽  
Lorenza Di Genova ◽  
Giovanni Dell’Isola ◽  
Elisabetta Mencaroni ◽  
Susanna Esposito
Keyword(s):  
Clinical Trials ◽  
Autism Spectrum Disorders ◽  
Gut Microbiota ◽  
Autism Spectrum ◽  
Current Evidence ◽  
Low Grade ◽  
Gut Dysbiosis ◽  
Children With Asd ◽  
Spectrum Disorders

In recent years, there has been an emerging interest in the possible role of the gut microbiota as a co-factor in the development of autism spectrum disorders (ASDs), as many studies have highlighted the bidirectional communication between the gut and brain (the so-called “gut-brain axis”). Accumulating evidence has shown a link between alterations in the composition of the gut microbiota and both gastrointestinal and neurobehavioural symptoms in children with ASD. The aim of this narrative review was to analyse the current knowledge about dysbiosis and gastrointestinal (GI) disorders in ASD and assess the current evidence for the role of probiotics and other non-pharmacological approaches in the treatment of children with ASD. Analysis of the literature showed that gut dysbiosis in ASD has been widely demonstrated; however, there is no single distinctive profile of the composition of the microbiota in people with ASD. Gut dysbiosis could contribute to the low-grade systemic inflammatory state reported in patients with GI comorbidities. The administration of probiotics (mostly a mixture of Bifidobacteria, Streptococci and Lactobacilli) is the most promising treatment for neurobehavioural symptoms and bowel dysfunction, but clinical trials are still limited and heterogeneous. Well-designed, randomized, placebo-controlled clinical trials are required to validate the effectiveness of probiotics in the treatment of ASD and to identify the appropriate strains, dose, and timing of treatment.

scholarly journals Induction of core symptoms of autism spectrum disorders by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys

2020 ◽  
Author(s):  
Shi-Hao Wu ◽  
Xiao Li ◽  
Dong-Dong Qin ◽  
Lin-Heng Zhang ◽  
Tian-Lin Cheng ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Rhesus Monkeys ◽  
Gene Editing ◽  
Autism Spectrum ◽  
Genetically Engineered ◽  
Behavioral Abnormalities ◽  
Spectrum Disorders ◽  
Rapid Generation ◽  
The Brain

AbstractAlthough CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders, whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined. Here we induced genetic mutations in MECP2, a critical gene linked to Rett syndrome (RTT) and autism spectrum disorders (ASDs), in the hippocampus (DG and CA1–4) of adolescent rhesus monkeys (Macaca mulatta) in vivo via adeno-associated virus (AAV)-delivered Staphylococcus aureus Cas9 with sgRNAs targeting MECP2. In comparison to monkeys injected with AAV-SaCas9 alone (n = 4), numerous autistic-like behavioral abnormalities were identified in the AAV-SaCas9-sgMECP2-injected monkeys (n = 7), including social interaction deficits, abnormal sleep patterns, insensitivity to aversive stimuli, abnormal hand motions and defective social reward behaviors. Furthermore, some aspects of ASDs and RTT, such as stereotypic behaviors, did not appear in the MECP2 gene-edited monkeys, suggesting that different brain areas likely contribute to distinct ASD symptoms. This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates, paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development.

Red blood cells in Rett syndrome: oxidative stress, morphological changes and altered membrane organization

2015 ◽  
Vol 396 (11) ◽  
pp. 1233-1240 ◽  
Author(s):  
Lucia Ciccoli ◽  
Claudio De Felice ◽  
Silvia Leoncini ◽  
Cinzia Signorini ◽  
Alessio Cortelazzo ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Morphological Changes ◽  
Single Gene ◽  
Neurodevelopmental Disorder ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Current Evidence ◽  
Loss Of Function ◽  
Beneficial Effects ◽  
Spectrum Disorders

Abstract In this review, we summarize the current evidence on the erythrocyte as a previously unrecognized target cell in Rett syndrome, a rare (1:10 000 females) and devastating neurodevelopmental disorder caused by loss-of-function mutations in a single gene (i.e. MeCP2, CDKL5, or rarely FOXG1). In particular, we focus on morphological changes, membrane oxidative damage, altered membrane fatty acid profile, and aberrant skeletal organization in erythrocytes from patients with typical Rett syndrome and MeCP2 gene mutations. The beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) are also summarized for this condition to be considered as a ‘model’ condition for autism spectrum disorders.

scholarly journals The Impact of Gut Microbiota-Derived Metabolites in Autism Spectrum Disorders

2021 ◽  
Vol 22 (18) ◽  
pp. 10052
Author(s):  
Lucía N. Peralta-Marzal ◽  
Naika Prince ◽  
Djordje Bajic ◽  
Léa Roussin ◽  
Laurent Naudon ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodevelopmental Disorders ◽  
Specific Treatment ◽  
Autism Spectrum ◽  
Microbial Composition ◽  
Host Interactions ◽  
Bidirectional Communication ◽  
Spectrum Disorders ◽  
The Impact ◽  
The Brain

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders characterised by behavioural impairment and deficiencies in social interaction and communication. A recent study estimated that 1 in 89 children have developed some form of ASD in European countries. Moreover, there is no specific treatment and since ASD is not a single clinical entity, the identification of molecular biomarkers for diagnosis remains challenging. Besides behavioural deficiencies, individuals with ASD often develop comorbid medical conditions including intestinal problems, which may reflect aberrations in the bidirectional communication between the brain and the gut. The impact of faecal microbial composition in brain development and behavioural functions has been repeatedly linked to ASD, as well as changes in the metabolic profile of individuals affected by ASD. Since metabolism is one of the major drivers of microbiome–host interactions, this review aims to report emerging literature showing shifts in gut microbiota metabolic function in ASD. Additionally, we discuss how these changes may be involved in and/or perpetuate ASD pathology. These valuable insights can help us to better comprehend ASD pathogenesis and may provide relevant biomarkers for improving diagnosis and identifying new therapeutic targets.

scholarly journals Genetic Approaches Using Zebrafish to Study the Microbiota–Gut–Brain Axis in Neurological Disorders

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 566
Author(s):  
Jae-Geun Lee ◽  
Hyun-Ju Cho ◽  
Yun-Mi Jeong ◽  
Jeong-Soo Lee
Keyword(s):  
Neurological Disorders ◽  
Genetic Model ◽  
Molecular Genetic ◽  
Autism Spectrum ◽  
Behavioral Abnormalities ◽  
Bidirectional Signaling ◽  
Intestinal Dysbiosis ◽  
The Central Nervous System ◽  
The Brain

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.

scholarly journals Administration of Bifidobacterium breve Improves the Brain Function of Aβ1-42-Treated Mice via the Modulation of the Gut Microbiome

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1602
Author(s):  
Guangsu Zhu ◽  
Jianxin Zhao ◽  
Hao Zhang ◽  
Wei Chen ◽  
Gang Wang
Keyword(s):  
Gut Microbiome ◽  
Dietary Intervention ◽  
Neuroprotective Effects ◽  
Bifidobacterium Breve ◽  
Beneficial Effects ◽  
Behavioral Abnormalities ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
The Brain ◽  
Fibronectin Type

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut–brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.

Differentiation of Healthy Individuals from Those with Autism Spectrum Disorders using Information Graph of Complementary Opposites

2020 ◽  
Keyword(s):  
Children With Autism ◽  
Autism Spectrum ◽  
Brain Signals ◽  
Three Stages ◽  
The Mean ◽  
Spectrum Disorders ◽  
Pediatric Psychiatry ◽  
The Brain ◽  
Optimal Feature ◽  
Information Graph

This study aimed to examine the brain signals of children with Autism Spectrum Disorder (ASD) and use a method according to the concept of complementary opposites to obtain the prominent features or a pattern of EEG signal that represents the biological characteristic of such children. In this study, 20 children with the mean±SD age of 8±5 years were divided into two groups of normal control (NC) and ASD. The diagnosis and approval of individuals in both groups were conducted by two experts in the field of pediatric psychiatry and neurology. The recording protocol was designed with the most accuracy; therefore, the brain signals were recorded with the least noise in the awake state of the individuals in both groups. Moreover, the recording was conducted in three stages from two channels (C3-C4) of EEG ( referred to as the central part of the brain) which were symmetrical in function. In this study, the Mandala method was adopted based on the concept of complementary opposites to investigate the features extracted from Mandala pattern topology and obtain new features and pseudo-patterns for the screening and early diagnosis of ASD. The optimal feature here was based on different stages of processing and statistical analysis of Pattern Detection Capability (PDC). The PDC is a biomarker derived from the Mandala pattern for differentiating the NC from ASD groups.

scholarly journals The Role of Iron in the Pathogenesis of Autism Spectrum Disorders in Children

2018 ◽  
Vol 17 (4) ◽  
pp. 281-286 ◽  
Author(s):  
Olga V. Kostina
Keyword(s):  
Autism Spectrum Disorders ◽  
Iron Metabolism ◽  
Biochemical Parameters ◽  
Children With Autism ◽  
Neuropsychiatric Disorders ◽  
Perinatal Period ◽  
Autism Spectrum ◽  
Spectrum Disorders ◽  
The Brain

The review presents an analysis of the mechanisms of iron effect on the brain development. The importance of iron deficiency in the perinatal period is considered as a risk factor for the development of neuropsychiatric disorders in children with autism spectrum disorders (ASDs). Possible causes of sideropenia are discussed; data on haematological and biochemical parameters characterizing iron metabolism in children with ASDs are presented. The demand for studying the role of iron metabolism imbalance in the development of neuropsychiatric disorders in order to clarify pathogenetic mechanisms of ASDs and to determine methods for their correction is emphasized.

The epigenetic regulation of synaptic genes contributes to the etiology of autism

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Annamaria Srancikova ◽  
Zuzana Bacova ◽  
Jan Bakos
Keyword(s):  
Epigenetic Regulation ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Prader Willi Syndrome ◽  
Epigenetic Mechanisms ◽  
Substantial Evidence ◽  
Autistic Symptoms ◽  
Spectrum Disorders ◽  
The Brain

Abstract Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins. Epigenetic causes of sex-dependent differences in the brain are analyzed in conjunction with the pathophysiology of autism spectrum disorders. Special attention is devoted to the epigenetic regulation of the melanoma-associated antigen-like gene 2 (MAGEL2) found in Prader-Willi syndrome, which is known to be accompanied by autistic symptoms.

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