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 Potential Novel Therapies for Neurodevelopmental Diseases Targeting Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Alexandrina S. Curpan ◽  
Alina-Costina Luca ◽  
Alin Ciobica
Keyword(s):  
Oxidative Stress ◽  
Neurodevelopmental Disorders ◽  
Antioxidant Properties ◽  
Autism Spectrum ◽  
Oxidative Status ◽  
Glutathione Level ◽  
Aspartate Receptor ◽  
Spectrum Disorders ◽  
The Impact ◽  
The Brain

Neurodevelopmental disorders are a category of diseases that is not yet fully understood. Due to their common traits and pathways, often it is difficult to differentiate between them based on their symptoms only. A series of hypotheses are trying to define their etiology, such as neuroinflammation, neurodegeneration, and immunology, but none have managed to explain their multifactorial manifestation. One feature that may link all theories is that of oxidative stress, with a redox imbalance as well as several other markers of oxidative damage (on lipids, proteins, and nucleic acids) being observed in both postmortem samples of the brain of patients with schizophrenia and autism spectrum disorders. However, the implication of oxidative stress in pathology is still distrustfully looked upon. For this purpose, in the current paper, we were interested in reviewing the implications of oxidative stress in these disorders as well as the impact of N-acetylcysteine on the oxidative status with a focus on the glutathione level and N-methyl-D-aspartate receptor. We were also interested in finding papers targeting the use of antioxidant properties of different plant extracts.

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.

scholarly journals Probiotics-Based Treatment as an Integral Approach for Alcohol Use Disorder in Alcoholic Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Catalina Fuenzalida ◽  
María Soledad Dufeu ◽  
Jaime Poniachik ◽  
Juan Pablo Roblero ◽  
Lucía Valenzuela-Pérez ◽  
...  
Keyword(s):  
Liver Disease ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Gut Microbiota ◽  
Liver Damage ◽  
Alcoholic Liver Disease ◽  
Alcohol Use Disorder ◽  
Autism Spectrum ◽  
Microbial Composition ◽  
The Impact

Alcoholic liver disease (ALD) is one of the leading causes of morbidity among adults with alcohol use disorder (AUD) worldwide. Its clinical course ranges from steatosis to alcoholic hepatitis, progressing to more severe forms of liver damage, such as cirrhosis and hepatocellular carcinoma. The pathogenesis of ALD is complex and diverse elements are involved in its development, including environmental factors, genetic predisposition, the immune response, and the gut-liver axis interaction. Chronic alcohol consumption induces changes in gut microbiota that are associated with a loss of intestinal barrier function and inflammatory responses which reinforce a liver damage progression triggered by alcohol. Alcohol metabolites such as acetaldehyde, lipid peroxidation-derived aldehyde malondialdehyde (MDA), and protein-adducts act as liver-damaging hepatotoxins and potentiate systemic inflammation. Additionally, ethanol causes direct damage to the central nervous system (CNS) by crossing the blood-brain barrier (BBB), provoking oxidative stress contributing to neuroinflammation. Overall, these processes have been associated with susceptibility to depression, anxiety, and alcohol craving in ALD. Recent evidence has shown that probiotics can reverse alcohol-induced changes of the microbiota and prevent ALD progression by restoring gut microbial composition. However, the impact of probiotics on alcohol consumption behavior has been less explored. Probiotics have been used to treat various conditions by restoring microbiota and decreasing systemic and CNS inflammation. The results of some studies suggest that probiotics might improve mental function in Alzheimer’s, autism spectrum disorder, and attenuated morphine analgesic tolerance. In this sense, it has been observed that gut microbiota composition alterations, as well as its modulation using probiotics, elicit changes in neurotransmitter signals in the brain, especially in the dopamine reward circuit. Consequently, it is not difficult to imagine that a probiotics-based complementary treatment to ALD might reduce disease progression mediated by lower alcohol consumption. This review aims to present an update of the pathophysiologic mechanism underlying the microbiota-gut-liver-brain axis in ALD, as well as to provide evidence supporting probiotic use as a complementary therapy to address alcohol consumption disorder and its consequences on liver damage.

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

Gut Microbiota and Gender in Autism Spectrum Disorders

2020 ◽  
Vol 16 ◽  
Author(s):  
Rafail I. Kushak ◽  
Harland S. Winter
Keyword(s):  
Gender Differences ◽  
Autism Spectrum Disorders ◽  
Gut Microbiota ◽  
Sex Hormones ◽  
Intestinal Microbiota ◽  
Autism Spectrum ◽  
Intestinal Microbiome ◽  
Gender Dimorphism ◽  
Spectrum Disorders ◽  
The Impact

: Gender dimorphism in autism spectrum disorders (ASD) is well known; however, the reasons for gender differences in autism are poorly understood. There are several hypotheses that might explain male prevalence in ASD including increased levels of androgens, “extreme male brain,” and a combination of elevated levels of prenatal testosterone in conjunction with prenatal stress. In this review, differences in the gut microbiome and metabolome in humans and animals are described to explain gender differences in individuals with ASD, effects on behavior and social interactions and the impact of antibiotics, probiotics and fecal transplants. The bidirectional relationship between sex hormones and intestinal microbiota could also be relevant. Such interactions have been described in autoimmune diseases, but thus far are not implicated in ASD. We hypothesize that similar cross-talk exists in ASD between gut microbiota and sex hormones. Since intestinal microbiota may affect behavior, it is possible that prevalence of ASD in boys may be associated with more significant changes in the intestinal microbiome than in affected girls.

scholarly journals Gut Microbiota and Their Neuroinflammatory Implications in Alzheimer’s Disease

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1765 ◽  
Author(s):  
Vo Giau ◽  
Si Wu ◽  
Angelo Jamerlan ◽  
Seong An ◽  
SangYun Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Bidirectional Communication ◽  
The Central Nervous System ◽  
Brain And Behavior ◽  
Underlying Mechanisms ◽  
And Behavior ◽  
The Impact ◽  
The Brain

The bidirectional communication between the central nervous system (CNS) and the gut microbiota plays a pivotal role in human health. Increasing numbers of studies suggest that the gut microbiota can influence the brain and behavior of patients. Various metabolites secreted by the gut microbiota can affect the cognitive ability of patients diagnosed with neurodegenerative diseases. Nearly one in every ten Korean senior citizens suffers from Alzheimer’s disease (AD), the most common form of dementia. This review highlights the impact of metabolites from the gut microbiota on communication pathways between the brain and gut, as well as the neuroinflammatory roles they may have in AD patients. The objectives of this review are as follows: (1) to examine the role of the intestinal microbiota in homeostatic communication between the gut microbiota and the brain, termed the microbiota–gut–brain (MGB) axis; (2) to determine the underlying mechanisms of signal dysfunction; and (3) to assess the impact of signal dysfunction induced by the microbiota on AD. This review will aid in understanding the microbiota of elderly people and the neuroinflammatory roles they may have in AD.

scholarly journals Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuki Murakami ◽  
Yukio Imamura ◽  
Kuniaki Saito ◽  
Daisuke Sakai ◽  
Jun Motoyama
Keyword(s):  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Kynurenine Pathway ◽  
Autism Spectrum ◽  
Behavioral Deficits ◽  
Diagnostic Biomarkers ◽  
Hyperactivity Disorder ◽  
Spectrum Disorders ◽  
Almost All ◽  
The Brain

Abstract Deleterious mutations in patchd1 domain containing 1 (PTCHD1) gene have been identified in patients with intellectual disability and/or autism spectrum disorder (ASD). To clarify the causal relationship between Ptchd1 deficiency and behavioral defects relevant to neurodevelopmental disorders, we generated global Ptchd1 knockout (KO) mice. Ptchd1 KO mice displayed hyperlocomotion, increased impulsivity, and lower recognition memory, which resemble attention-deficit hyperactivity disorder (ADHD)-like behaviors. Acute or chronic treatment with atomoxetine ameliorated almost all behavioral deficits in Pthcd1 KO mice. We next determined possible involvement of the kynurenine pathway (KP) metabolites in neurodevelopmental disorders in Ptchd1 KO mice and assessed the potential of KP metabolites as biomarkers for ADHD and/or ASD. Ptchd1 KO mice showed drastic changes in KP metabolite concentrations in the serum and the brain, indicating that the activated KP is associated with ADHD-like behaviors. Our findings indicate that Ptchd1 KO mice can be used as an animal model of human ADHD and/or ASD, and KP metabolites are potential diagnostic biomarkers for neurodevelopmental disorders.

scholarly journals The Multifaceted Roles of Primary Cilia in the Development of the Cerebral Cortex

2021 ◽  
Vol 9 ◽  
Author(s):  
Kerstin Hasenpusch-Theil ◽  
Thomas Theil
Keyword(s):  
Cerebral Cortex ◽  
Neurodevelopmental Disorders ◽  
Primary Cilia ◽  
Autism Spectrum ◽  
Multiple Roles ◽  
Axon Pathfinding ◽  
Spectrum Disorders ◽  
Circuit Formation ◽  
Multiple Signaling ◽  
The Brain

The primary cilium, a microtubule based organelle protruding from the cell surface and acting as an antenna in multiple signaling pathways, takes center stage in the formation of the cerebral cortex, the part of the brain that performs highly complex neural tasks and confers humans with their unique cognitive capabilities. These activities require dozens of different types of neurons that are interconnected in complex ways. Due to this complexity, corticogenesis has been regarded as one of the most complex developmental processes and cortical malformations underlie a number of neurodevelopmental disorders such as intellectual disability, autism spectrum disorders, and epilepsy. Cortical development involves several steps controlled by cell–cell signaling. In fact, recent findings have implicated cilia in diverse processes such as neurogenesis, neuronal migration, axon pathfinding, and circuit formation in the developing cortex. Here, we will review recent advances on the multiple roles of cilia during cortex formation and will discuss the implications for a better understanding of the disease mechanisms underlying neurodevelopmental disorders.

scholarly journals Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment

2020 ◽  
Vol 57 (12) ◽  
pp. 5026-5043 ◽  
Author(s):  
Shan Liu ◽  
Jiguo Gao ◽  
Mingqin Zhu ◽  
Kangding Liu ◽  
Hong-Liang Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Gut Dysbiosis ◽  
Bidirectional Communication ◽  
Significant Research ◽  
Novel Therapeutic Strategies ◽  
The Brain ◽  
Brain Homeostasis ◽  
Gut Microbiota Composition

Abstract Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

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