scholarly journals A Novel and Reliable Rat Model of Autism

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhaoyao Qi ◽  
Mengke Lyu ◽  
Liping Yang ◽  
Haiyan Yuan ◽  
Yun Cao ◽  
...  
Keyword(s):  
Animal Model ◽  
Gut Microbiota ◽  
Rat Model ◽  
Immune Activation ◽  
Fecal Microbiota Transplantation ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Structural Validity ◽  
Pregnant Rat ◽  
Sample Extract

Background: Autism spectrum disorders (ASD) is a complex neurodevelopmental disorder that lacks an ideal animal model to recapitulate the disease state of ASD. Previous studies have reported that transplanting gut microbiota of ASD patients into pregnant mice is sufficient to promote the changes of autism-like behavior in offspring. This study aims to explore whether fecal microbiota transplantation (FMT) can be used as a new method to establish the ASD animal model.Methods: We transplanted the fecal sample extract of ASD children into pregnant rats (rFMT) repeatedly to establish an ASD rat model (oFMT) and compare it with the classical valproic acid (VPA) model (oVPA).Results: First, we reveal that oFMT shows hypoevolutism and typical behavioral characteristics of ASD, consistent with the previous study. Second, the gut microbiota of oFMT mainly consists of Firmicutes and Bacteroidetes, recapitulating the abnormal gut microbiota of ASD. In oFMT, the abundance of Lactobacillus and Collinsella increased (Lactobacillus: oFMT 60.16%, oVPA 64.13%, oCON 40.11%; Collinsella: oFMT 3.73%, oVPA 1.39%, oCON 1.28%), compared with oVPA, gut microbiota also showed high consistency. Third, the expression of 5-hydroxytryptamine (5-HT) in oFMT serum increased, γ-aminobutyric acid (GABA) and norepinephrine (NE) in oFMT serum decreased. Fourth, the gut microbiota of oFMT also has some ASD characteristic gut microbiota not found in oVPA. Fifth, pregnant rat with VPA showed significant immune activation, while those with FMT showed relatively minor immune activation.Limitations: Although the mechanism of establishing FMT autism rat model (oFMT) has not clearly defined, the data show that the model has high structural validity, and FMT model is likely to be a new and reliable potential animal model of ASD, and will have potential value in studying gut microbiota of ASD.Conclusions: The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD.

scholarly journals The development of animal models for autism: A gene-environment approach

2021 ◽  
Author(s):  
◽  
Peter Ranger
Keyword(s):  
Animal Models ◽  
Prenatal Exposure ◽  
Environmental Risk ◽  
Rat Model ◽  
Immune Activation ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Maternal Immune Activation ◽  
Gene Environment ◽  
Social Communicative

<p>Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder characterised by social, communicative, and behavioural deficits. Despite decades of research in this field, effective pharmacological treatments for ASD are still lacking and better animal models for this disorder are urgently needed. Although it is now well understood that both genetic and environmental influences play a role in the aetiology of ASD, most existing animal models for this disorder only take into account one of these aetiological contributors and have largely ignored investigating an interaction. The main aim of this thesis was to develop a novel animal model for ASD that demonstrated higher construct validity than traditional models by using a gene-environment approach. To this aim, two previously established environmental risk factor-based models for ASD were each combined with a genetic rat model that mimicked a genotype associated with ASD. Specifically, a maternal immune activation model (modelled via prenatal administration of lipopolysaccharide) and a prenatal exposure to valproate model (modelled via prenatal administration of valproate) were both combined with a serotonin transporter (SERT) knockout rat model. Next, experimental rats were investigated in a variety of paradigms designed to detect behavioural, biochemical, and immunological outcomes related to ASD. This thesis tested the hypothesis that rats with a genetically compromised SERT function would be more vulnerable to the impacts of the two environmental risk factors. Collectively, the data from this thesis show that rats with a genetically compromised SERT function are not more vulnerable to the impacts of a maternal immune activation or prenatal exposure to VPA. In fact, at least with regards to prenatal exposure to valproate, rats with a compromised SERT function actually appeared more resilient to ASD-like outcomes.</p>

scholarly journals The development of animal models for autism: A gene-environment approach

2021 ◽  
Author(s):  
◽  
Peter Ranger
Keyword(s):  
Animal Models ◽  
Prenatal Exposure ◽  
Environmental Risk ◽  
Rat Model ◽  
Immune Activation ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Maternal Immune Activation ◽  
Gene Environment ◽  
Social Communicative

<p>Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder characterised by social, communicative, and behavioural deficits. Despite decades of research in this field, effective pharmacological treatments for ASD are still lacking and better animal models for this disorder are urgently needed. Although it is now well understood that both genetic and environmental influences play a role in the aetiology of ASD, most existing animal models for this disorder only take into account one of these aetiological contributors and have largely ignored investigating an interaction. The main aim of this thesis was to develop a novel animal model for ASD that demonstrated higher construct validity than traditional models by using a gene-environment approach. To this aim, two previously established environmental risk factor-based models for ASD were each combined with a genetic rat model that mimicked a genotype associated with ASD. Specifically, a maternal immune activation model (modelled via prenatal administration of lipopolysaccharide) and a prenatal exposure to valproate model (modelled via prenatal administration of valproate) were both combined with a serotonin transporter (SERT) knockout rat model. Next, experimental rats were investigated in a variety of paradigms designed to detect behavioural, biochemical, and immunological outcomes related to ASD. This thesis tested the hypothesis that rats with a genetically compromised SERT function would be more vulnerable to the impacts of the two environmental risk factors. Collectively, the data from this thesis show that rats with a genetically compromised SERT function are not more vulnerable to the impacts of a maternal immune activation or prenatal exposure to VPA. In fact, at least with regards to prenatal exposure to valproate, rats with a compromised SERT function actually appeared more resilient to ASD-like outcomes.</p>

scholarly journals Potential Effect of Probiotics on the Modulating of Gut Microbiota in Autism Spectrum Disorders (ASD)

2021 ◽  
pp. 26-38
Author(s):  
Wed Alluhaim ◽  
Manal M. Alkhulaifi ◽  
Godfred A. Menezes
Keyword(s):  
Gut Microbiota ◽  
Animal Studies ◽  
Fecal Microbiota Transplantation ◽  
Social Withdrawal ◽  
Neurodevelopmental Disorder ◽  
Potential Effect ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
The Body ◽  
Bacterial Strains

Microbiota is the summation of all microorganisms living in the body. The alteration in microbiota can lead to chronic diseases, however; colonization with different commensal bacteria can correct these deficits. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by inadequate communication skills and social withdrawal and its etiology is uncertain. Typical gastrointestinal (GI) disorders symptoms are associated with ASD, in a prevalence range from 23% to 70%. The method of communication between the brain and the gut microbiota is likely the microbiota-gut-brain axis. Therefore, intervention studies have been published based on the use of prebiotics, probiotics and fecal microbiota transplantation (FMT). In this review, the possible correlation between gut microbiota and ASD is demonstrated. Additionally, how probiotics and microbial fecal microbiota transplantation (FMT) could modulate the gut microbiota and might represent a potential therapy for patients with ASD. Nearly all the GI functions postulated to be affected in ASD are improved by probiotics in animal studies. (FMT) ensures the transfer of several hundred bacterial strains, as opposed to probiotic therapy where only certain bacterial strains are supplemented. For ASD patients with dysbiosis, FMT is an interesting new therapeutic choice that could be considered.

scholarly journals Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation

2021 ◽  
Vol 11 ◽  
Author(s):  
Paulina Żebrowska ◽  
Izabela Łaczmańska ◽  
Łukasz Łaczmański
Keyword(s):  
Pediatric Patients ◽  
Fecal Microbiota Transplantation ◽  
Neurodevelopmental Disorder ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
Long Term Effects ◽  
Gi Symptoms ◽  
Inflammatory Bowel ◽  
Age Range

Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.

scholarly journals Altered Gut Microbiota in Korean Children with Autism Spectrum Disorders

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3300
Author(s):  
Sungji Ha ◽  
Donghun Oh ◽  
Sunghee Lee ◽  
Jaewan Park ◽  
Jaeun Ahn ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodevelopmental Disorder ◽  
Critical Role ◽  
Short Chain Fatty Acids ◽  
Bioinformatic Analysis ◽  
Autism Spectrum ◽  
Korean Children ◽  
Children With Asd ◽  
Genetic Information Processing ◽  
Behavioral Impairments

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and behavioral impairments. Recent studies have suggested that gut microbiota play a critical role in ASD pathogenesis. Herein, we investigated the fecal microflora of Korean ASD children to determine gut microbiota profiles associated with ASD. Specifically, fecal samples were obtained from 54 children with ASD and 38 age-matched children exhibiting typical development. Systematic bioinformatic analysis revealed that the composition of gut microbiota differed between ASD and typically developing children (TDC). Moreover, the total amounts of short-chain fatty acids, metabolites produced by bacteria, were increased in ASD children. At the phylum level, we found a significant decrease in the relative Bacteroidetes abundance of the ASD group, whereas Actinobacteria abundance was significantly increased. Furthermore, we found significantly lower Bacteroides levels and higher Bifidobacterium levels in the ASD group than in the TDC group at the genus level. Functional analysis of the microbiota in ASD children predicted that several pathways, including genetic information processing and amino acid metabolism, can be associated with ASD pathogenesis. Although more research is needed to determine whether the differences between ASD and TDC are actually related to ASD pathogenesis, these results provide further evidence of altered gut microbiota in children with ASD, possibly providing new perspectives on the diagnosis and therapeutic approaches for ASD patients.

scholarly journals Do the Bugs in Your Gut Eat Your Memories? Relationship between Gut Microbiota and Alzheimer’s Disease

2020 ◽  
Vol 10 (11) ◽  
pp. 814
Author(s):  
Emily M. Borsom ◽  
Keehoon Lee ◽  
Emily K. Cope
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Dietary Intervention ◽  
Fecal Microbiota Transplantation ◽  
Neurological Diseases ◽  
Amyloid Β ◽  
Reproductive Organs ◽  
Fecal Microbiota ◽  
Autism Spectrum

The human microbiota is composed of trillions of microbial cells inhabiting the oral cavity, skin, gastrointestinal (GI) tract, airways, and reproductive organs. The gut microbiota is composed of dynamic communities of microorganisms that communicate bidirectionally with the brain via cytokines, neurotransmitters, hormones, and secondary metabolites, known as the gut microbiota–brain axis. The gut microbiota–brain axis is suspected to be involved in the development of neurological diseases, including Alzheimer’s disease (AD), Parkinson’s disease, and Autism Spectrum Disorder. AD is an irreversible, neurodegenerative disease of the central nervous system (CNS), characterized by amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Microglia and astrocytes, the resident immune cells of the CNS, play an integral role in AD development, as neuroinflammation is a driving factor of disease severity. The gut microbiota–brain axis is a novel target for Alzheimer’s disease therapeutics to modulate critical neuroimmune and metabolic pathways. Potential therapeutics include probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention. This review summarizes our current understanding of the role of the gut microbiota–brain axis and neuroinflammation in the onset and development of Alzheimer’s disease, limitations of current research, and potential for gut microbiota–brain axis targeted therapies.

scholarly journals The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4497
Author(s):  
Michelle A. Chernikova ◽  
Genesis D. Flores ◽  
Emily Kilroy ◽  
Jennifer S. Labus ◽  
Emeran A. Mayer ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Preclinical Research ◽  
Gastrointestinal Problems ◽  
The Brain

Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.

scholarly journals Genetic screening of autism, a neurodevelopmental disorder: A review

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1864-1869
Author(s):  
Ranjana Shaw ◽  
Tamalika Chakraborty ◽  
Dipanjan Mandal
Keyword(s):  
Animal Model ◽  
Mutational Analysis ◽  
Genetic Manipulation ◽  
Neurodevelopmental Disorder ◽  
Disease Model ◽  
Disease Onset ◽  
Autism Spectrum ◽  
Future Research ◽  
Genetic Constitution ◽  
Human Genes

Neurodevelopmental disorders are conditions that arise from aberrant encephalon magnification and development, are perennial, crippling illness. Autism spectrum disorder (autism) is a common neurodevelopmental disability characterized by motor, social, cognitive function, stereotypies. This study aimed to investigate the genetic constitution of autism, an animal model named zebrafish serves as an indispensable tool for this purpose. Zebrafish is a highly gregarious species that acts as a suitable animal model system that affects convivial functions such as autism. Since transparent embryos are developed externally in zebrafish, it enables to conduct pharmacological screens for recognition of minute molecules along with genetic manipulation, facilitated through the CRISPR/Cas9 gene-editing technologies, enabling the screening of the developing nervous system directly, large progenies, and substantial tractability. Mutational analysis of the genetic function has been used to suppress or express mutations in zebrafish homologs of human genes for the direct expression of human genes bearing mutations cognate to a neurodevelopmental disorder. Two areas of future research are addressed through the ease and relative speed of conducting experiments in zebrafish, which includes environmental factors contributing to disease onset, and screening for novel therapeutic compounds. This study found that zebrafish have become available for cell-based analysis and have been used for the prosperous modelling of autism. Continued innovations in zebrafish genetic implements will continue to make it a captivating neurological disease model.

scholarly journals Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Li ◽  
Hongyan Chen ◽  
Yi Cheng ◽  
Fenghua Xu ◽  
Guangcong Ruan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Symptoms ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
Autism Symptoms ◽  
Clinical Trial Registry ◽  
Children With Asd ◽  
Gi Symptoms

Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of Eubacterium coprostanoligenes pre-FMT was positively correlated with high GSRS scores, whereas a decrease in Eubacterium coprostanoligenes abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets Eubacterium coprostanoligenes that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).

scholarly journals Gut microbiota on gender bias in autism spectrum disorder

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Xia Hao ◽  
Jiao Pan ◽  
Xiumei Gao ◽  
Shiyu Zhang ◽  
Yue Li
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Specific Treatment ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Communication Disorder ◽  
Gender Dimorphism ◽  
Men And Women

AbstractAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Its three core symptoms are social communication disorder, communication disorder, narrow interest and stereotyped repetitive behavior. The proportion of male and female autistic patients is 4:1. Many researchers have studied this phenomenon, but the mechanism is still unclear. This review mainly discusses the related mechanism from the perspective of gut microbiota and introduces the influence of gut microbiota on the difference of ASD between men and women, as well as how gut microbiota may affect the gender dimorphism of ASD through metabolite of microbiota, immunity, and genetics, which provide some useful information for those who are interested in this research and find more gender-specific treatment for autistic men and women.

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