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1.
NPJ Biofilms Microbiomes ; 8(1): 91, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400799

RESUMO

Growing evidence suggests altered oral and gut microbiota in autism spectrum disorder (ASD), but little is known about the alterations and roles of phages, especially within the oral microbiota in ASD subjects. We enrolled ASD (n = 26) and neurotypical subjects (n = 26) with their oral hygiene controlled, and the metagenomes of both oral and fecal samples (n = 104) are shotgun-sequenced and compared. We observe extensive and diverse oral phageome comparable to that of the gut, and clear signals of mouth-to-gut phage strain transfer within individuals. However, the overall phageomes of the two sites are widely different and show even less similarity in the oral communities between ASD and control subjects. The ASD oral phageome exhibits significantly reduced abundance and alpha diversity, but the Streptococcal phages there are atypically enriched, often dominating the community. The over-representation of Streptococcal phages is accompanied by enriched oral Streptococcal virulence factors and Streptococcus bacteria, all exhibiting a positive correlation with the severity of ASD clinical manifestations. These changes are not observed in the parallel sampling of the gut flora, suggesting a previously unknown oral-specific association between the excessive Streptococcal phage enrichment and ASD pathogenesis. The findings provide new evidence for the independent microbiome-mouth-brain connection, deepen our understanding of how the growth dynamics of bacteriophages and oral microbiota contribute to ASD, and point to novel effective therapeutics.


Assuntos
Transtorno do Espectro Autista , Bacteriófagos , Microbioma Gastrointestinal , Fagos de Streptococcus , Humanos , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/microbiologia , Boca/microbiologia , Bacteriófagos/genética
2.
Nutrients ; 14(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36296908

RESUMO

As the largest "immune organ" of human beings, the gut microbiota is symbiotic and mutually beneficial with the human host, playing multiple physiological functions. Studies have long shown that dysbiosis of gut microbiota is associated with almost all human diseases, mainly including type II diabetes, cancers, neurodegenerative diseases, autism spectrum disorder, and kidney diseases. As a novel and potential biological medicine for disease prevention, intervention and drug sensitization, the gut microbiota has attracted more and more attention recently. Although the gut microbiota is a comprehensive microbial community, several star bacteria have emerged as possible tools to fight against various diseases. This review aims to elucidate the relevance of gut microbiota dysbiosis with disease occurrence and progression, and mainly summarizes four well-known genera with therapeutic and sensitizing potential, Akkermansia, Bifidobacterium, Lactobacillus and Parabacteroides, thoroughly elucidate their potential value as biological drugs to treat diverse disease.


Assuntos
Transtorno do Espectro Autista , Produtos Biológicos , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Disbiose/microbiologia , Transtorno do Espectro Autista/microbiologia
3.
Int J Mol Sci ; 23(15)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35955962

RESUMO

Autism spectrum disorder (ASD) is often associated with several intestinal and/or metabolic disorders as well as neurological manifestations such as epilepsy (ASD-E). Those presenting these neuropathological conditions share common aspects in terms of gut microbiota composition. The use of microbiota intervention strategies may be an approach to consider in the management of these cases. We describe the case of a 17-year-old girl affected by ASD, reduced growth, neurological development delay, mutations in the PGM1 and EEF1A2 genes (in the absence of clinically manifested disease) and, intestinal disorders such as abdominal pain and diarrhea associated with weight loss. As she demonstrated poor responsiveness to the therapies provided, we attempted two specific dietary patterns: a ketogenic diet, followed by a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, with the aim of improving her neurological, metabolic, and intestinal symptoms through modulation of the gut microbiota's composition. The ketogenic diet (KD) provided a reduction in Firmicutes, Bacteroidetes, and Proteobacteria. Although her intestinal symptoms improved, KD was poorly tolerated. On the other hand, the passage to a low FODMAPs diet produced a significant improvement in all neurological, intestinal, and metabolic symptoms and was well-tolerated. The following gut microbiota analysis showed reductions in Actinobacteria, Firmicutes, Lactobacilli, and Bifidobacteria. The alpha biodiversity was consistently increased and the Firmicutes/Bacteroidetes ratio decreased, reducing the extent of fermentative dysbiosis. Gut microbiota could be a therapeutic target to improve ASD-related symptoms. Further studies are needed to better understand the correlation between gut microbiota composition and ASD, and its possible involvement in the physiopathology of ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Epilepsia , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Adolescente , Transtorno do Espectro Autista/microbiologia , Dieta com Restrição de Carboidratos , Dissacarídeos/farmacologia , Epilepsia/terapia , Feminino , Humanos , Síndrome do Intestino Irritável/microbiologia , Monossacarídeos/farmacologia , Oligossacarídeos/farmacologia , Fator 1 de Elongação de Peptídeos
4.
Gut Microbes ; 14(1): 2104089, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35876011

RESUMO

Accumulating evidence suggests that gut microbiota as a critical mediator of gut-brain axis plays an important role in human health. Altered gut microbial profiles have been implicated in increasing the vulnerability of psychiatric disorders, such as autism, depression, and schizophrenia. However, the cellular and molecular mechanisms underlying the association remain unknown. Here, we modified the gut microbiome with antibiotics in newborn mice, and found that gut microbial alteration induced behavioral impairment by decreasing adult neurogenesis and long-term potentiation of synaptic transmission, and altering the gene expression profile in hippocampus. Reconstitution with normal gut flora produced therapeutic effects against both adult neurogenesis and behavioral deficits in the dysbiosis mice. Furthermore, our results show that circulating metabolites changes mediate the effect of gut dysbiosis on hippocampal plasticity and behavior outcomes. Elevating the serum 4-methylphenol, a small aromatic metabolite produced by gut bacteria, was found to induce autism spectrum disorder (ASD)-like behavior impairment and hippocampal dysfunction. Together our finding demonstrates that early-life gut dysbiosis and its correlated metabolites change contribute to hippocampal dysfunction and behavior impairment, hence highlight the potential microbiome-mediated therapies for treating psychiatric disorders.


Assuntos
Transtorno do Espectro Autista , Microbioma Gastrointestinal , Adulto , Animais , Transtorno do Espectro Autista/microbiologia , Disbiose/microbiologia , Hipocampo/metabolismo , Humanos , Metaboloma , Camundongos
5.
Int J Mol Sci ; 23(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35163286

RESUMO

The high prevalence of gastrointestinal (GI) disorders among autism spectrum disorder (ASD) patients has prompted scientists to look into the gut microbiota as a putative trigger in ASD pathogenesis. Thus, many studies have linked the gut microbial dysbiosis that is frequently observed in ASD patients with the modulation of brain function and social behavior, but little is known about this connection and its contribution to the etiology of ASD. This present review highlights the potential role of the microbiota-gut-brain axis in autism. In particular, it focuses on how gut microbiota dysbiosis may impact gut permeability, immune function, and the microbial metabolites in autistic people. We further discuss recent findings supporting the possible role of the gut microbiome in initiating epigenetic modifications and consider the potential role of this pathway in influencing the severity of ASD. Lastly, we summarize recent updates in microbiota-targeted therapies such as probiotics, prebiotics, dietary supplements, fecal microbiota transplantation, and microbiota transfer therapy. The findings of this paper reveal new insights into possible therapeutic interventions that may be used to reduce and cure ASD-related symptoms. However, well-designed research studies using large sample sizes are still required in this area of study.


Assuntos
Transtorno do Espectro Autista/microbiologia , Eixo Encéfalo-Intestino/fisiologia , Microbioma Gastrointestinal/fisiologia , Encéfalo/metabolismo , Suplementos Nutricionais , Disbiose/metabolismo , Transplante de Microbiota Fecal , Gastroenteropatias/metabolismo , Humanos , Microbiota , Prebióticos , Probióticos
6.
PLoS One ; 17(2): e0263109, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35202432

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a neurological and developmental condition that begins in infancy or earlier and lasts through the individual's lifetime. The aetiology and mechanisms of ASD are not yet fully understood, and current treatment comprises mainly education and rehabilitation, without significant improvement in the core symptoms. Recent studies suggest that microbiota change in children with ASD after the ingestion of probiotics may improve the balance of microbiota and thus ASD symptoms. OBJECTIVE: The objectives of this study are to evaluate the efficacy of probiotics on the symptoms of children with ASD and the possible mechanisms involved. METHODS: This is a prospective controlled trial. A total of 160 children with ASD will be stratified and allocated to placebo and probiotics groups randomised according to the severity of their ASD symptoms. The probiotics group will be given probiotics supplements orally twice a day for 3 months and the control group will be given a placebo at the same amount, in addition to the baseline therapy of education and rehabilitation. All the children will be evaluated systematically by using different scales, questionnaires before, during, and after 3 months' treatment, as well as 3 months after discontinuation. The potential impact of probiotics on immunity and inflammation, metabolism, and metagenome will also be investigated. DISCUSSION: Our previous study showed that the abundance of intestinal flora was greatly different in children with ASD, and that Bifidobacterium was associated with the severity of ASD. In the present study, we will investigate the impact of probiotics supplementation on the symptoms of Children with ASD, with the purpose of evaluating the possible therapeutic effects of additives on ASD and of providing a reference for clinical treatment. The results will help to disclose as yet unknown relationship between probiotics and ASD. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR-2000037941).


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Metagenoma/genética , Probióticos/administração & dosagem , Transtorno do Espectro Autista/microbiologia , Transtorno do Espectro Autista/patologia , Bifidobacterium/genética , Bifidobacterium/patogenicidade , Criança , Pré-Escolar , Feminino , Microbioma Gastrointestinal/genética , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/imunologia , Inflamação/microbiologia , Masculino , Metagenoma/efeitos dos fármacos , Placebos , Probióticos/efeitos adversos
7.
J Autism Dev Disord ; 52(3): 1374-1387, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33948825

RESUMO

Previous studies have reported dysbiosis in the gut microbiota (GM) of children with autism spectrum disorders (ASD), which may be a determining factor on child development through the microbiota-gut-brain axis. However, it is not clear if there is a specific group of dysbiotic bacteria in ASD. The aim of this study was to carry out a meta-analysis on the studies that analyze GM in children with ASD. 18 studies fulfilled our selection criteria. Our results showed a lower relative abundance of Streptococcus (SMD+ = - 0.999; 95% CI - 1.549, - 0.449) and Bifidobacterium genera (SMD+ = - 0.513; 95% CI - 0.953, - 0.073) in children with ASD. Overall, the Bifidobacterium genera is involved. However, differences found between studies are attributed to factors such as reporting bias.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Microbioma Gastrointestinal , Transtorno do Espectro Autista/microbiologia , Bactérias , Criança , Disbiose/microbiologia , Humanos
8.
Int Microbiol ; 25(2): 267-274, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34562157

RESUMO

Accumulating evidence has pointed out that the gut-brain axis plays important roles in the etiology of autism spectrum disorder (ASD). Gut dysbiosis was reported in both ASD human patients and animal models. Dip2a was identified as a human ASD candidate gene. Deletion of Dip2a led to dendritic spine dysfunction and autistic-like behaviors in mice. To further investigate if Dip2a deletion leads to gut dysbiosis, we used 16S rDNA sequencing to study the gut microbiota in Dip2a KO mice. In both co-housed and separated breeding conditions, deletion of Dip2a could affect the gut microbiome composition. The probiotic bacteria, Lactobacillus and Bifidobacterium, became less abundant, while some potentially harmful bacteria, Alistipes, Lachnospiraceae_NK4A136_group, Clostridium, Desulfovibrio, and Enterorhabdus, became more abundant. We further found that probiotic treatment could help to reconstitute the gut microbiome composition in Dip2a KO mice. Altogether, these data showed DIP2A is required for the proper composition of gut microbiota, and the probiotics have potential roles in rectifying the gut microbiota in Dip2a KO mice.


Assuntos
Transtorno do Espectro Autista , Microbioma Gastrointestinal , Probióticos , Animais , Transtorno do Espectro Autista/microbiologia , Disbiose/microbiologia , Humanos , Camundongos , Camundongos Knockout , Proteínas Nucleares , Projetos Piloto
9.
Gut ; 71(5): 910-918, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34312160

RESUMO

OBJECTIVE: The gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD. DESIGN: We performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model. RESULTS: ASD and chronological age had the most significant and largest impacts on children's faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum. CONCLUSIONS: Gut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.


Assuntos
Transtorno do Espectro Autista , Microbioma Gastrointestinal , Microbiota , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/microbiologia , Bactérias/genética , Biomarcadores , Criança , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos
10.
Dev Med Child Neurol ; 64(3): 296-304, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34523735

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by variable impairment of cognitive function and interpersonal relationships. Furthermore, some individuals with ASD have gastrointestinal disorders that have been correlated with impairments in intestinal microbiota. Gut microbiota are important not only for intestinal health, but also for many other functions including food digestion, energy production, immune system regulation, and, according to current data, behavior. Disruption of the indigenous microbiota, microbial dysbiosis (imbalance between microorganisms present in the gut), overgrowth of potentially pathogenic microorganisms, a less diverse microbiome, or lower levels of beneficial bacteria in children with ASD can affect behavior. Metabolome analysis in children with ASD has identified perturbations in multiple metabolic pathways that might be associated with cognitive functions. Recent studies have shown that the intestinal microbiome provides environmental signals that can modify host response to stimuli by modifying the host epigenome, which affects DNA methylation, histone modification, and non-coding RNAs. The most studied microbiota-produced epigenetic modifiers are short-chain fatty acids, although other products of intestinal microbiota might also cause epigenetic modifications in the host's DNA. Here we review evidence suggesting that epigenetic alterations caused by modification of gene expression play an important role in understanding ASD.


Assuntos
Transtorno do Espectro Autista , Disbiose , Epigenoma , Microbioma Gastrointestinal , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/microbiologia , Criança , Disbiose/genética , Disbiose/metabolismo , Disbiose/microbiologia , Epigenoma/genética , Humanos
11.
Immunity ; 55(1): 145-158.e7, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34879222

RESUMO

Children with autism spectrum disorders often display dysregulated immune responses and related gastrointestinal symptoms. However, the underlying mechanisms leading to the development of both phenotypes have not been elucidated. Here, we show that mouse offspring exhibiting autism-like phenotypes due to prenatal exposure to maternal inflammation were more susceptible to developing intestinal inflammation following challenges later in life. In contrast to its prenatal role in neurodevelopmental phenotypes, interleukin-17A (IL-17A) generated immune-primed phenotypes in offspring through changes in the maternal gut microbiota that led to postnatal alterations in the chromatin landscape of naive CD4+ T cells. The transfer of stool samples from pregnant mice with enhanced IL-17A responses into germ-free dams produced immune-primed phenotypes in offspring. Our study provides mechanistic insights into why children exposed to heightened inflammation in the womb might have an increased risk of developing inflammatory diseases in addition to neurodevelopmental disorders.


Assuntos
Transtorno do Espectro Autista/imunologia , Linfócitos T CD4-Positivos/imunologia , Cromatina/metabolismo , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Interleucina-17/metabolismo , Intestinos/imunologia , Transtornos do Neurodesenvolvimento/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Animais , Transtorno do Espectro Autista/microbiologia , Criança , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Feminino , Humanos , Imunização , Inflamação/microbiologia , Camundongos , Transtornos do Neurodesenvolvimento/microbiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/microbiologia
12.
Sci Rep ; 11(1): 24274, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34931007

RESUMO

The early-life modifications of intestinal microbiota may impact children's subsequent emotional and cognitive development. Studies show that some bacteria species in gut microbiota, and the lack of others, may play a key role in autism spectrum disorders (ASD) development. Fecal samples were obtained from three groups of children: 16 healthy, 24 with allergies (ALG), and 33 with ASD (probiotics and non-probiotics users). The analysis was carried out according to the KyberKompakt Pro protocol. We observed a significantly higher level of Klebsiella spp. in the healthy children from the non-probiotics group, considering three groups. In the same group, Bifidobacterium spp. the level was lower in ASD compared to neurotypical individuals. In healthy children who did not use probiotics, strong positive correlations were observed in E. coli and Enterococcus spp. and Bacteroides and Klebsiella spp., and a negative correlation for Akkermansia muciniphila with both Klebsiella spp. and Bacteroides spp. In the ASD group who take probiotics, a strongly negative correlation was observed in Lactobacillus spp., and both Faecalibacterium prausnitzii and Akkermansia muciniphila levels. In the ALG group, the strongest, negative correlation was found between Enterococcus spp. and Lactobacillus spp. as in Akkermansia muciniphila and Bifidobacterium spp. The simple commercial test revealed minor differences in the composition of intestinal microorganisms between children with autism spectrum disorders and neurotypical peers.


Assuntos
Transtorno do Espectro Autista/microbiologia , Microbioma Gastrointestinal/genética , Microbiota , Akkermansia , Bacteroides , Índice de Massa Corporal , Criança , Pré-Escolar , Enterococcus , Escherichia coli , Faecalibacterium , Fezes , Feminino , Humanos , Hipersensibilidade , Inflamação , Intestinos/microbiologia , Klebsiella , Masculino , Microbiologia , Análise de Componente Principal , Probióticos
13.
Nutrients ; 13(12)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34960049

RESUMO

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.


Assuntos
Transtorno do Espectro Autista/microbiologia , Eixo Encéfalo-Intestino/fisiologia , Encéfalo/microbiologia , Gastroenteropatias/psicologia , Microbioma Gastrointestinal/fisiologia , Animais , Gastroenteropatias/microbiologia , Humanos
14.
Cell Mol Life Sci ; 79(1): 46, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936034

RESUMO

Gastrointestinal (GI) problems and microbiota alterations have been frequently reported in autism spectrum disorders (ASD). In addition, abnormal perinatal trace metal levels have been found in ASD. Accordingly, mice exposed to prenatal zinc deficiency display features of ASD-like behavior. Here, we model GI development using 3D intestinal organoids grown under zinc-restricted conditions. We found significant morphological alterations. Using proteomic approaches, we identified biological processes affected by zinc deficiency that regulate barrier permeability and pro-inflammatory pathways. We confirmed our results in vivo through proteomics studies and investigating GI development in zinc-deficient mice. These show altered GI physiology and pro-inflammatory signaling, resulting in chronic systemic and neuroinflammation, and gut microbiota composition similar to that reported in human ASD cases. Thus, low zinc status during development is sufficient to compromise intestinal barrier integrity and activate pro-inflammatory signaling, resulting in changes in microbiota composition that may aggravate inflammation, altogether mimicking the co-morbidities frequently observed in ASD.


Assuntos
Transtorno do Espectro Autista , Gastroenteropatias , Doenças Neuroinflamatórias , Zinco/deficiência , Animais , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/microbiologia , Feminino , Gastroenteropatias/metabolismo , Gastroenteropatias/microbiologia , Microbioma Gastrointestinal , Trato Gastrointestinal/crescimento & desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/microbiologia , Organoides , Proteômica
15.
Nutrients ; 13(11)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34836074

RESUMO

Children with autism spectrum disorder (ASD) report a higher frequency and severity of gastrointestinal disorders (GID) than typically developing (TD) children. GID-associated discomfort increases feelings of anxiety and frustration, contributing to the severity of ASD. Emerging evidence supports the biological intersection of neurodevelopment and microbiome, indicating the integral contribution of GM in the development and function of the nervous system, and mental health, and disease balance. Dysbiotic GM could be a contributing factor in the pathogenesis of GID in children with ASD. High-fat diets may modulate GM through accelerated growth of bile-tolerant bacteria, altered bacterial ratios, and reduced bacterial diversity, which may increase the risk of GID. Notably, saturated fatty acids are considered to have a pronounced effect on the increase of bile-tolerant bacteria and reduction in microbial diversity. Additionally, omega-3 exerts a favorable impact on GM and gut health due to its anti-inflammatory properties. Despite inconsistencies in the data elaborated in the review, the dietary fat composition, as part of an overall dietary intervention, plays a role in modulating GID, specifically in ASD, due to the altered microbiome profile. This review emphasizes the need to conduct future experimental studies investigating the effect of diets with varying fatty acid compositions on GID-specific microbiome profiles in children with ASD.


Assuntos
Transtorno do Espectro Autista/microbiologia , Gorduras na Dieta/farmacologia , Disbiose/psicologia , Gastroenteropatias/psicologia , Microbioma Gastrointestinal/efeitos dos fármacos , Eixo Encéfalo-Intestino/efeitos dos fármacos , Criança , Dieta/efeitos adversos , Dieta/psicologia , Humanos
16.
Nutrients ; 13(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684301

RESUMO

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.


Assuntos
Transtorno do Espectro Autista/microbiologia , Microbioma Gastrointestinal , Adolescente , Biodiversidade , Criança , Pré-Escolar , Ácidos Graxos/metabolismo , Feminino , Humanos , Masculino , Filogenia , Análise de Componente Principal , República da Coreia , Estatísticas não Paramétricas
17.
Nutrients ; 13(10)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34684493

RESUMO

Autism is a group of neurodevelopmental disorders, characterized by early onset difficulties in social communication and restricted, repetitive behaviors and interests. It is characterized by familial aggregation, suggesting that genetic factors play a role in disease development, in addition to developmentally early environmental factors. Here, we review the role of the gut microbiome in autism, as it has been characterized in case-control studies. We discuss how methodological differences may have led to inconclusive or contradictory results, even though a disproportion between harmful and beneficial bacteria is generally described in autism. Furthermore, we review the studies concerning the effects of gut microbial-based and dietary interventions on autism symptoms. Also, in this case, the results are not comparable due to the lack of standardized methods. Therefore, autism-specific microbiome signatures and, consequently, possible microbiome-oriented interventions are far from being recognized. We argue that a multi-omic longitudinal implementation may be useful to study metabolic changes connected to microbiome changes.


Assuntos
Transtorno do Espectro Autista/microbiologia , Encéfalo/microbiologia , Microbioma Gastrointestinal/fisiologia , Estudos de Casos e Controles , Humanos
18.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205336

RESUMO

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.


Assuntos
Cognição/fisiologia , Microbioma Gastrointestinal/fisiologia , Doenças Neurodegenerativas/microbiologia , Neurotransmissores/fisiologia , Doença de Alzheimer/microbiologia , Animais , Ansiedade/microbiologia , Transtorno do Espectro Autista/microbiologia , Encéfalo/fisiopatologia , Depressão/microbiologia , Disbiose/fisiopatologia , Humanos , Doença de Parkinson/microbiologia , Esquizofrenia/microbiologia
19.
Nutrients ; 13(5)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34062986

RESUMO

Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3-20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 1010 CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted.


Assuntos
Transtorno do Espectro Autista/terapia , Ocitocina/administração & dosagem , Probióticos/administração & dosagem , Adolescente , Transtorno do Espectro Autista/microbiologia , Transtorno do Espectro Autista/psicologia , Biomarcadores/análise , Criança , Pré-Escolar , Clostridiales , Terapia Combinada , Método Duplo-Cego , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Mediadores da Inflamação/sangue , Lactobacillus plantarum , Masculino , Projetos Piloto , Cognição Social , Resultado do Tratamento , Adulto Jovem
20.
Front Immunol ; 12: 676255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113350

RESUMO

Autism spectrum disorders (ASD) are serious, highly variable neurodevelopmental disorders, commonly characterized by the manifestation of specific behavioral abnormalities, such as stereotypic behaviors and deficits in social skills, including communication. Although the neurobiological basis for ASD has attracted attention in recent decades, the role of microglial cells, which are the main resident myeloid cell population in the brain, is still controversial and underexplored. Microglia play several fundamental roles in orchestrating brain development and homeostasis. As such, alterations in the intrinsic functions of these cells could be one of the driving forces responsible for the development of various neurodevelopmental disorders, including ASD. Microglia are highly sensitive to environmental cues. Amongst the environmental factors known to influence their intrinsic functions, the gut microbiota has emerged as a central player, controlling both microglial maturation and activation. Strikingly, there is now compelling data suggesting that the intestinal microbiota can play a causative role in driving the behavioural changes associated with ASD. Not only is intestinal dysbiosis commonly reported in ASD patients, but therapies targeting the microbiome can markedly alleviate behavioral symptoms. Here we explore the emerging mechanisms by which altered microglial functions could contribute to several major etiological factors of ASD. We then demonstrate how pre- and postnatal environmental stimuli can modulate microglial cell phenotype and function, underpinning the notion that reciprocal interactions between microglia and intestinal microbes could play a crucial role in ASD aetiology.


Assuntos
Transtorno do Espectro Autista/etiologia , Microbioma Gastrointestinal/fisiologia , Microglia/fisiologia , Animais , Transtorno do Espectro Autista/imunologia , Transtorno do Espectro Autista/microbiologia , Disbiose , Humanos
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