Altered gut microbiota correlates with behavioral problems but not gastrointestinal symptoms in individuals with autism

Chen, Yu-Chieh; Lin, Hon‐Yi; Chien, Yi‐Ling; Tung, Yung-Liang; Ni, Yen‐Hsuan; Gau, Susan Shur-Fen

doi:10.1016/j.bbi.2022.08.015

Cited by 33 publications

(10 citation statements)

References 194 publications

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“…The finding of lower microbiome diversity in the ASD population compared to controls was consistent with some studies ( 20 , 45 , 46 ), but it was also contrary to others ( 21 , 23 , 47 ). In the De Angelis study, children aged 4–10 were from Italy.…”

Section: Discussionsupporting

confidence: 90%

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

Phan,

Calvo,

Nair

et al. 2024

mSystems

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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.

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Section: Discussionsupporting

confidence: 90%

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

Phan,

Calvo,

Nair

et al. 2024

mSystems

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“…Butyricicoccus was also inversely associated with AD in a cross-sectional study, which is consistent with our findings [ 12 ]. Approximately 70% of individuals with autism spectrum disorder (ASD) exhibit comorbid symptoms of anxiety, and the findings from a published article confirming the decreased relative abundance of ErysipelotrichaceaeUCG003 in ASD patients further support our research results indicating a negative correlation between ErysipelotrichaceaeUCG003 and AD [ 30 ]. In a study examining SAD, the control group exhibited higher levels of the positive bacteria Parasutterella compared to the anxiety group.…”

Section: Discussionsupporting

confidence: 82%

Association between gut microbiota and anxiety disorders: a bidirectional two-sample mendelian randomization study

Li,

Fan,

Wang

et al. 2024

BMC Psychiatry

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Background There are many articles reporting that the component of intestinal microbiota implies a link to anxiety disorders (AD), and the brain-gut axis is also a hot topic in current research. However, the specific relevance between gut microbiota and AD is uncertain. We aimed to investigate causal relationship between gut microbiota and AD by using bidirectional Mendelian randomization (MR). Methods Genetic instrumental variable (IV) for the gut microbiota were obtained from a genome-wide association study (GWAS) involving 18,340 participants. Summary data for AD were derived from the GWAS and included 158,565 cases and 300,995 controls. We applied the inverse variance weighted (IVW) method as the main analysis. Cochran’s Q values was computed to evaluate the heterogeneity among IVs. Sensitivity analyses including intercept of MR-Egger method and MR-PRESSO analysis were used to test the horizontal pleiotropy. Result We discovered 9 potential connections between bacterial traits on genus level and AD. Utilizing the IVW method, we identified 5 bacterial genera that exhibited a direct correlation with the risk of AD: genus Eubacteriumbrachygroup, genus Coprococcus3, genus Enterorhabdus, genus Oxalobacter, genus Ruminiclostridium6. Additionally, we found 4 bacterial genera that exhibited a negative association with AD: genus Blautia, genus Butyricicoccus, genus Erysipelotrichaceae-UCG003 and genus Parasutterella. The associations were confirmed by the sensitivity analyses. Conclusion Our study found a causal relation between parts of the gut microbiota and AD. Further randomized controlled trials are crucial to elucidate the positive effects of probiotics on AD and their particular protection systems.

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“…Butyricicoccus was also inversely associated with AD in a cross-sectional study, which is consistent with our ndings [12] . Approximately 70% of individuals with autism spectrum disorder (ASD) exhibit comorbid symptoms of anxiety, and the ndings from a published article con rming the decreased relative abundance of ErysipelotrichaceaeUCG003 in ASD patients further support our research results indicating a negative correlation between ErysipelotrichaceaeUCG003 and AD [33] . In a study examining social anxiety disorder, the control group exhibited higher levels of the bene cial bacteria Parasutterella compared to the anxiety group.…”

Section: Discussionsupporting

confidence: 79%

Association between gut microbiota and anxiety disorders: a bidirectional two-sample Mendelian randomization study

jianbing,

changhe,

jiaqi

et al. 2023

Preprint

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Background There are many articles reporting that the component of intestinal microbiota implies a link to anxiety disorders (AD), and the brain-gut axis is also a hot topic in current research. However, the specific relevance between gut microbiota and AD is uncertain. We aimed to investigate causal relationship between gut microbiota and AD by using bidirectional Mendelian randomization (MR). Methods Genetic instrumental variable (IV) for the gut microbiota were obtained from a genome-wide association study (GWAS) involving 18,340 participants. Summary data for AD were derived from the GWAS and included 158,565 cases and 300,995 controls. We applied the inverse variance weighting (IVW) method as the main analysis. To ensure the robustness of the results, we further executed weighted median method and MR-Egger regression to evaluate potential horizontal pleiotropy. Result We discovered 16 potential connections between bacterial traits and AD. Utilizing the IVW method, we identified 7 species that exhibited a direct correlation with the risk of AD: class Negativicutes, genus Eubacteriumbrachygroup, genus Coprococcus3, genus Enterorhabdus, genus Oxalobacter, genus Ruminiclostridium6, order Selenomonadales. Additionally, we found 9 species that exhibited a negative association with AD: class Methanobacteria, family Methanobacteriaceae, family Porphyromonadaceae, genus Blautia, genus Butyricicoccus, genus Erysipelotrichaceae-UCG003, genus Parasutterella, order Methanobacteriales, phylum Proteobacteria. Conclusion Our study found a causal relation between parts of the gut microbiota and AD. Further randomized controlled trials are crucial to elucidate the protective effects of probiotics on AD and their particular protection systems.

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Altered gut microbiota correlates with behavioral problems but not gastrointestinal symptoms in individuals with autism

Cited by 33 publications

References 194 publications

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

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

Association between gut microbiota and anxiety disorders: a bidirectional two-sample mendelian randomization study

Association between gut microbiota and anxiety disorders: a bidirectional two-sample Mendelian randomization study

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