Modulation of Gut Microbiome and Autism Symptoms of ASD Children Supplemented with Biological Response Modifier: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study.

The etiology and mechanisms of autism and autism spectrum disorder (ASD) are not yet fully understood. There is currently no treatment for ASD for providing significant improvement in core symptoms. Recent studies suggest, however, that ASD is associated with gut dysbiosis, indicating that modulation of gut microbiota in children with ASD may thus reduce the manifestation of ASD symptoms. The aim of this pilot study (prospective randomized, double-blinded, placebo-controlled) was to evaluate efficacy of the biological response modifier Juvenil in modulating the microbiome of children with ASD and, in particular, whether Juvenil is able to alleviate the symptoms of ASD. In total, 20 children with ASD and 12 neurotypical children were included in our study. Supplementation of ASD children lasted for three months. To confirm Juvenil's impact on the gut microbiome, stool samples were collected from all children and the microbiome's composition was analyzed. This pilot study demonstrated that the gut microbiome of ASD children differed significantly from that of healthy controls and was converted by Juvenil supplementation toward a more neurotypical microbiome that positively modulated children's autism symptoms.

Revealing the gut microbiome mystery: A meta-analysis revealing differences between individuals with autism spectrum disorder and neurotypical children.

The brain-gut axis intricately links gut microbiota (GM) dysbiosis to the development or worsening of autism spectrum disorder (ASD). However, the precise GM composition in ASD and the effectiveness of probiotics are unclear. To address this, we performed a thorough meta-analysis of 28 studies spanning PubMed, PsycINFO, Web of Science, Scopus, and MEDLINE, involving 1,256 children with ASD and 1042 neurotypical children, up to February 2024. Using Revman 5.3, we analyzed the relative abundance of 8 phyla and 64 genera. While individuals with ASD did not exhibit significant differences in included phyla, they exhibited elevated levels of Parabacteroides, Anaerostipes, Faecalibacterium, Clostridium, Dorea, Phascolarctobacterium, Lachnoclostridium, Catenibacterium, and Collinsella along with reduced percentages of Barnesiella, Odoribacter, Paraprevotella, Blautia, Turicibacter, Lachnospira, Pseudomonas, Parasutterella, Haemophilus, and Bifidobacterium. Notably, discrepancies in Faecalibacterium, Clostridium, Dorea, Phascolarctobacterium, Catenibacterium, Odoribacter, and Bifidobacterium persisted even upon systematic exclusion of individual studies. Consequently, the GM of individuals with ASD demonstrates an imbalance, with potential increases or decreases in both beneficial and harmful bacteria. Therefore, personalized probiotic interventions tailored to ASD specifics are imperative, rather than a one-size-fits-all approach.

Comprehensive Analysis of Gut Microbiota Composition and Functional Metabolism in Children with Autism Spectrum Disorder and Neurotypical Children: Implications for Sex-Based Differences and Metabolic Dysregulation.

This study aimed to investigate the gut microbiota composition in children with autism spectrum disorder (ASD) compared to neurotypical (NT) children, with a focus on identifying potential differences in gut bacteria between these groups. The microbiota was analyzed through the massive sequencing of region V3-V4 of the 16S RNA gene, utilizing DNA extracted from stool samples of participants. Our findings revealed no significant differences in the dominant bacterial phyla (Firmicutes, Bacteroidota, Actinobacteria, Proteobacteria, Verrucomicrobiota) between the ASD and NT groups. However, at the genus level, notable disparities were observed in the abundance of Blautia, Prevotella, Clostridium XI, and Clostridium XVIII, all of which have been previously associated with ASD. Furthermore, a sex-based analysis unveiled additional discrepancies in gut microbiota composition. Specifically, three genera (Megamonas, Oscilibacter, Acidaminococcus) exhibited variations between male and female groups in both ASD and NT cohorts. Particularly noteworthy was the exclusive presence of Megamonas in females with ASD. Analysis of predicted metabolic pathways suggested an enrichment of pathways related to amine and polyamine degradation, as well as amino acid degradation in the ASD group. Conversely, pathways implicated in carbohydrate biosynthesis, degradation, and fermentation were found to be underrepresented. Despite the limitations of our study, including a relatively small sample size (30 ASD and 31 NT children) and the utilization of predicted metabolic pathways derived from 16S RNA gene analysis rather than metagenome sequencing, our findings contribute to the growing body of evidence suggesting a potential association between gut microbiota composition and ASD. Future research endeavors should focus on validating these findings with larger sample sizes and exploring the functional significance of these microbial differences in ASD. Additionally, there is a critical need for further investigations to elucidate sex differences in gut microbiota composition and their potential implications for ASD pathology and treatment.

Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of Lactiplantibacillus plantarum intervention.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic Lactiplantibacillus plantarum PS128 (PS128) alleviates ASD symptoms in children. However, the mechanism underlying this improvement in ASD-associated behaviors remains unclear. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of PS128 in vivo. Overall, we showed that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, PS128 alters the gut microbiota composition and increases the abundance of Bifidobacterium spp. and PS128-induced changes in Bifidobacterium abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.

Ketogenic Diet Induced Shifts in the Gut Microbiome Associate with Changes to Inflammatory Cytokines and Brain-Related miRNAs in Children with Autism Spectrum Disorder.

In this interventional pilot study, we investigated the effects of a modified ketogenic diet (KD) on children with autism spectrum disorder (ASD). We previously observed improved behavioral symptoms in this cohort following the KD; this trial was registered with Clinicaltrials.gov (NCT02477904). This report details the alterations observed in the microbiota, inflammation markers, and microRNAs of seven children following a KD for a duration of 4 months. Our analysis included blood and stool samples, collected before and after the KD. After 4 months follow up, we found that the KD led to decreased plasma levels of proinflammatory cytokines (IL-12p70 and IL-1b) and brain-derived neurotrophic factor (BDNF). Additionally, we observed changes in the gut microbiome, increased expression of butyrate kinase in the gut, and altered levels of BDNF-associated miRNAs in the plasma. These cohort findings suggest that the KD may positively influence ASD sociability, as previously observed, by reducing inflammation, reversing gut microbial dysbiosis, and impacting the BDNF pathway related to brain activity.

Prospective association of the infant gut microbiome with social behaviors in the ECHO consortium.

BACKGROUND: Identifying modifiable risk factors of autism spectrum disorders (ASDs) may inform interventions to reduce financial burden. The infant/toddler gut microbiome is one such feature that has been associated with social behaviors, but results vary between cohorts. We aimed to identify consistent overall and sex-specific associations between the early-life gut microbiome and autism-related behaviors. METHODS: Utilizing the Environmental influences on Children Health Outcomes (ECHO) consortium of United States (U.S.) pediatric cohorts, we gathered data on 304 participants with fecal metagenomic sequencing between 6-weeks to 2-years postpartum (481 samples). ASD-related social development was assessed with the Social Responsiveness Scale (SRS-2). Linear regression, PERMANOVA, and Microbiome Multivariable Association with Linear Models (MaAsLin2) were adjusted for sociodemographic factors. Stratified models estimated sex-specific effects. RESULTS: Genes encoding pathways for synthesis of short-chain fatty acids were associated with higher SRS-2 scores, indicative of ASDs. Fecal concentrations of butyrate were also positively associated with ASD-related SRS-2 scores, some of which may be explained by formula use. LIMITATIONS: The distribution of age at outcome assessment differed in the cohorts included, potentially limiting comparability between cohorts. Stool sample collection methods also differed between cohorts. Our study population reflects the general U.S. population, and thus includes few participants who met the criteria for being at high risk of developing ASD. CONCLUSIONS: Our study is among the first multicenter studies in the U.S. to describe prospective microbiome development from infancy in relation to neurodevelopment associated with ASDs. Our work contributes to clarifying which microbial features associate with subsequent diagnosis of neuropsychiatric outcomes. This will allow for future interventional research targeting the microbiome to change neurodevelopmental trajectories.

Gut microbiota composition links to variation in functional domains across psychiatric disorders.

OBJECTIVE: Changes in microbial composition are observed in various psychiatric disorders, but their specificity to certain symptoms or processes remains unclear. This study explores the associations between the gut microbiota composition and the Research Domain Criteria (RDoC) domains of functioning, representing symptom domains, specifically focusing on stress-related and neurodevelopmental disorders in patients with and without psychiatric comorbidity. METHODS: The gut microbiota was analyzed in 369 participants, comprising 272 individuals diagnosed with a mood disorder, anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, and/or substance use disorder, as well as 97 psychiatrically unaffected individuals. The RDoC domains were estimated using principal component analysis (PCA) with oblique rotation on a range of psychiatric, psychological, and personality measures. Associations between the gut microbiota and the functional domains were assessed using multiple linear regression and permanova, adjusted for age, sex, diet, smoking, medication use and comorbidity status. RESULTS: Four functional domains, aligning with RDoC's negative valence, social processes, cognitive systems, and arousal/regulatory systems domains, were identified. Significant associations were found between these domains and eight microbial genera, including associations of negative valence with the abundance of the genera Sellimonas, CHKCI001, Clostridium sensu stricto 1, Oscillibacter, and Flavonifractor; social processes with Sellimonas; cognitive systems with Sporobacter and Hungatella; and arousal/regulatory systems with Ruminococcus torques (all pFDR < 0.05). CONCLUSION: Our findings demonstrate associations between the gut microbiota and the domains of functioning across patients and unaffected individuals, potentially mediated by immune-related processes. These results open avenues for microbiota-focused personalized interventions, considering psychiatric comorbidity. However, further research is warranted to establish causality and elucidate mechanistic pathways.

Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.

Dietary flavonoids modulate the gut microbiota: A new perspective on improving autism spectrum disorder through the gut-brain axis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unknown etiology. It is associated with various factors and causes great inconvenience to the patient's life. The gut-brain axis (GBA), which serves as a bidirectional information channel for exchanging information between the gut microbiota and the brain, is vital in studying many neurodegenerative diseases. Dietary flavonoids provide anti-inflammatory and antioxidant benefits, as well as regulating the structure and function of the gut microbiota. The occurrence and development of ASD are associated with dysbiosis of the gut microbiota. Modulation of gut microbiota can effectively improve the severity of ASD. This paper reviews the links between gut microbiota, flavonoids, and ASD, focusing on the mechanism of dietary flavonoids in regulating ASD through the GBA.

Interactions-based classification of a single microbial sample.

To address the limitation of overlooking crucial ecological interactions due to relying on single time point samples, we developed a computational approach that analyzes individual samples based on the interspecific microbial relationships. We verify, using both numerical simulations as well as real and shuffled microbial profiles from the human oral cavity, that the method can classify single samples based on their interspecific interactions. By analyzing the gut microbiome of people with autistic spectrum disorder, we found that our interaction-based method can improve the classification of individual subjects based on a single microbial sample. These results demonstrate that the underlying ecological interactions can be practically utilized to facilitate microbiome-based diagnosis and precision medicine.

Infant microbes and metabolites point to childhood neurodevelopmental disorders.

This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.

Precision synbiotics increase gut microbiome diversity and improve gastrointestinal symptoms in a pilot open-label study for autism spectrum disorder.

The efficacy of prebiotics and probiotics (synbiotics when combined) to improve symptoms associated with autism spectrum disorder (ASD) has shown considerable inter-study variation, likely due to the complex, heterogeneous nature of the disorder and its associated behavioral, developmental, and gastrointestinal symptoms. Here, we present a precision synbiotic supplementation study in 296 children and adults diagnosed with ASD versus 123 age-matched neurotypical controls. One hundred seventy ASD participants completed the study. Baseline and post-synbiotic assessment of ASD and gastrointestinal (GI) symptoms and deep metagenomic sequencing were performed. Within the ASD cohort, there were significant differences in microbes between subpopulations based on the social responsiveness scale (SRS2) survey (Prevotella spp., Bacteroides, Fusicatenibacter, and others) and gluten and dairy-free diets (Bifidobacterium spp., Lactococcus, Streptococcus spp., and others). At the baseline, the ASD cohort maintained a lower taxonomic alpha diversity and significant differences in taxonomic composition, metabolic pathways, and gene families, with a greater proportion of potential pathogens, including Shigella, Klebsiella, and Clostridium, and lower proportions of beneficial microbes, including Faecalibacterium compared to controls. Following the 3-month synbiotic supplementation, the ASD cohort showed increased taxonomic alpha diversity, shifts in taxonomy and metabolic pathway potential, and improvements in some ASD-related symptoms, including a significant reduction in GI discomfort and overall improved language, comprehension, cognition, thinking, and speech. However, the open-label study design may include some placebo effects. In summary, we found that precision synbiotics modulated the gut microbiome and could be used as supplementation to improve gastrointestinal and ASD-related symptoms. IMPORTANCE: Autism spectrum disorder (ASD) is prevalent in 1 out of 36 children in the United States and contributes to health, financial, and psychological burdens. Attempts to identify a gut microbiome signature of ASD have produced varied results. The limited pre-clinical and clinical population sizes have hampered the success of these trials. To understand the microbiome associated with ASD, we employed whole metagenomic shotgun sequencing to classify microbial composition and genetic functional potential. Despite being one of the most extensive ASD post-synbiotic assessment studies, the results highlight the complexity of performing such a case-control supplementation study in this population and the potential for a future therapeutic approach in ASD.

A metagenome-wide association study of gut microbiome in patients with AMD, ASD, RA, T2D & VKH diseases.

Clinical studies have already illustrated the associations between gut microbes and diseases, yet fundamental questions remain unclear that how we can universalize this knowledge. Considering the important role of human gut microbial composition in maintaining overall health, it is important to understand the microbial diversity and altered disease conditions of the human gut. Metagenomics provides a way to analyze and understand the microbes and their role in a community manner. It provides qualitative as well as quantitative measurements, in terms of relative abundance. Various studies are already going on to find out the association between microbes and diseases; still, the mined knowledge is limited. Considering the current scenario, using the targeted metagenomics approach, we analyzed the gut microbiome of 99 samples from healthy and diseased individuals. Our metagenomic analysis mainly targeted five diseased microbiomes (i.e., Age-related macular degeneration, Autism spectrum disorder, Rheumatoid arthritis, Type 2 diabetes and Vogt-Koyanagi harada), with compare to healthy microbiome, and reported disease-associated microbiome shift in different conditions.

Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis.

Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring's gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.

Alterations in fecal virome and bacteriome virome interplay in children with autism spectrum disorder.

Emerging evidence suggests autism spectrum disorder (ASD) is associated with altered gut bacteria. However, less is known about the gut viral community and its role in shaping microbiota in neurodevelopmental disorders. Herein, we perform a metagenomic analysis of gut-DNA viruses in 60 children with ASD and 64 age- and gender-matched typically developing children to investigate the effect of the gut virome on host bacteria in children with ASD. ASD is associated with altered gut virome composition accompanied by the enrichment of Clostridium phage, Bacillus phage, and Enterobacteria phage. These ASD-enriched phages are largely associated with disrupted viral ecology in ASD. Importantly, changes in the interplay between the gut bacteriome and virome seen in ASD may influence the encoding capacity of microbial pathways for neuroactive metabolite biosynthesis. These findings suggest an impaired bacteriome-virome ecology in ASD, which sheds light on the importance of bacteriophages in pathogenesis and the development of microbial therapeutics in ASD.

The Microbiome in Child and Adolescent Psychiatry.

Recent research has increasingly emphasized the function of the microbiome in human health. The gut microbiome is essential for digesting food and seems to play a vital role in mental health as well. This review briefly overviews the gut microbiome and its interplay with the central nervous system. We then summarize some of the latest findings on the possible role of the microbiome in psychiatric disorders in children and adolescents. In particular, we focus on autism spectrum disorder, attention-deficit/hyperactivity disorder, anorexia nervosa, bipolar disorder, and major depressive disorder. Although the role of microbiota in mental development and health still needs to be researched intensively, it has become increasingly apparent that the impact of microbiota must be considered to better understand psychiatric disorders.

Prenatal caffeine exposure induces autism-like behaviors in offspring under a high-fat diet via the gut microbiota-IL-17A-brain axis.

Prenatal caffeine exposure (PCE) is a significant contributor to intrauterine growth retardation (IUGR) in offspring, which has been linked to an increased susceptibility to autism spectrum disorder (ASD) later in life. Additionally, a high-fat diet (HFD) has been shown to exacerbate ASD-like behaviors, but the underlying mechanisms remain unclear. In this study, we first noted in the rat model of IUGR induced by PCE that male PCE offspring exhibited typical ASD-like behaviors post-birth, in contrast to their female counterparts. The female PCE offspring demonstrated only reduced abilities in free exploration and spatial memory. Importantly, both male and female PCE offspring displayed ASD-like behaviors when exposed to HFD. We further observed that PCE + HFD offspring exhibited damaged intestinal mucus barriers and disturbed gut microbiota, resulting in an increased abundance of Escherichia coli (E. coli). The induced differentiation of colonic Th17 cells by E. coli led to an increased secretion of IL-17A, which entered the hippocampus through peripheral circulation and caused synaptic damage in hippocampal neurons, ultimately resulting in ASD development. Our strain transplantation experiment suggested that E. coli-mediated increase of IL-17A may be the core mechanism of ASD with a fetal origin. In conclusion, PCE and HFD are potential risk factors for ASD, and E. coli-mediated IL-17A may play a crucial role in fetal-originated ASD through the gut-brain axis.

Effects of whey protein supplementation on gut microbiota of Wistar rats with valproic acid-induced autism symptoms.

Aim: To evaluate the effects of whey protein (WP) supplementation (1.24 mg/g, 24 days) in rats with autism spectrum disorder (ASD) induced by valproic acid (400 mg/kg, single dose). Materials & methods: Wistar rats (14 days old) were divided into four groups: control, ASD, ASD plus WP and WP. Results: WP increased bacterial diversity and the number of colonies. Bacteria from the Firmicutes phylum were predominantly found in the supplemented groups (p < 0.05). WP also improved the animals' memory in the Y-maze test and decreased the time that male animals spent in the 'solitary chamber' (p < 0.05). Conclusion: WP supplementation positively influenced gut microbiota, along with memory.

Thousands of bacteria live in the human intestine. These bacteria help with many functions in the body and are so important that they can communicate with the brain. When the types and abundance of these bacteria change, brain activity can also change. This may be the case in some children with autism spectrum disorder (ASD), who may have an increase in harmful types of bacteria and a decrease in beneficial types of bacteria in the gut. Whey protein is a commonly used protein supplement for muscle growth. However, many studies have shown its benefits for gut bacteria. The authors investigated the effects of whey protein in animals with symptoms of ASD and showed that supplementation with whey protein increased the number of beneficial bacteria. In addition, the rats given whey protein had better memory. ASD-induced rats were less sociable, spending more time by themselves. However, male animals treated with whey protein spent less time alone. Supplementation with whey protein was beneficial for gut bacteria and memory in rats.

[Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions]. / Darmmikrobiota und Autismus-Spektrum-Störungen: Ein Überblick zu Zusammenhängen und möglichen Implikationen für therapeutische Interventionen.

Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions Abstract: At the beginning of research on microbiota, researchers focused mainly on the role of microbiota dysbiosis in the development of gastrointestinal diseases. However, over the last years, researchers have also identified correlations with other physical processes and neuropsychiatric diseases such as autism spectrum disorder. These correlations are believed to be at least partly mediated through the brain-gut-microbiome axis. An altered composition of microbiota in patients with autism spectrum disorder was detected compared to healthy controls. Today, the discussion centers around a possible systemic impact of the metabolites of some microbiota or microbiota-induced chronic inflammatory processes on the brain (mediated through the brain-gut-microbiome axis) as an underlying mechanism. Still, the specific underlying mechanisms remain largely unknown, so conclusions on therapeutic implications are difficult to determine. Here, we describe some promising approaches to improving autistic behavior through dietary changes, the use of prebiotics and probiotics, stool transplantation from healthy controls, and restricted absorbance of certain metabolites. We need further clinical studies of high quality to fully understand the pathophysiology of autism spectrum disorder and to improve diagnostic and therapeutic strategies.

Liposomal Epigallocatechin-3-Gallate for the Treatment of Intestinal Dysbiosis in Children with Autism Spectrum Disorder: A Comprehensive Review.

Autism Spectrum Disorder (ASD) is characterized by varying degrees of difficulty in social interaction and communication. These deficits are often associated with gastrointestinal symptoms, indicating alterations in both intestinal microbiota composition and metabolic activities. The intestinal microbiota influences the function and development of the nervous system. In individuals with ASD, there is an increase in bacterial genera such as Clostridium, as well as species involved in the synthesis of branched-chain amino acids (BCAA) like Prevotella copri. Conversely, decreased amounts of Akkermansia muciniphila and Bifidobacterium spp. are observed. Epigallocatechin-3-gallate (EGCG) is one of the polyphenols with the greatest beneficial activity on microbial growth, and its consumption is associated with reduced psychological distress. Therefore, the objective of this review is to analyze how EGCG and its metabolites can improve the microbial dysbiosis present in ASD and its impact on the pathology. The analysis reveals that EGCG inhibits the growth of pathogenic bacteria like Clostridium perfringens and Clostridium difficile. Moreover, it increases the abundance of Bifidobacterium spp. and Akkermansia spp. As a result, EGCG demonstrates efficacy in increasing the production of metabolites involved in maintaining epithelial integrity and improving brain function. This identifies EGCG as highly promising for complementary treatment in ASD.