The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder

Al-Harthi, Amani M.; Alhazmi, Safiah; Alburae, Najla Ali; Bahieldin, Ahmed

doi:10.3390/ijms23031363

Cited by 52 publications

(43 citation statements)

References 141 publications

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“…Cobalamin or B12 deficiency can cause increased homocysteine, or hyperhomocysteinemia, which occurs commonly in patients with inflammatory bowel disease (63). Similar changes in the gut microbial ecosystem in ASD studies showed the implications of gut dysbiosis in the production and utilization of vitamins such as B12 (64). The use of comparisons between AS and ASD that lead to microbial dysbiosis and metabolic disparities has the potential to identify what changes in the metabolome and microbiome contribute to disease severity.…”

Section: Discussionmentioning

confidence: 86%

Unique features of the gut microbiome characterized in animal models of Angelman Syndrome

Beitnere

Vilanova-Cuevas

Christian

et al. 2022

Preprint

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A large subset of patients with Angelman syndrome (AS) suffer from concurrent gastrointestinal (GI) issues, including constipation, poor feeding, and reflux. AS is caused by the loss of ubiquitin ligase E3A (UBE3A) gene expression in the brain. Clinical features of AS, which include developmental delays, intellectual disability, microcephaly, and seizures, are primarily due to the deficient expression or function of the maternally inherited UBE3A allele. The association between neurodevelopmental delay and GI disorders is part of the increasing evidence suggesting a link between the brain and the gut microbiome via the microbiota-gut-brain (MGB) axis. To investigate the associations between colonization of the gut microbiota in AS, we characterized the fecal microbiome in three animal models of AS containing maternal deletions of Ube3A, including mouse, rat, and pig, using 16S ribosomal RNA amplicon sequencing. Overall changes in the microbial composition of all three animal models of AS in both the phylum and genus levels of bacterial abundance were identified. Specific bacterial groups were significantly increased across all animal models, including: Lachnospiraceae Incertae sedis, Desulfovibrios sp., and Odoribacter, which have been correlated with neuropsychiatric disorders. Taken together, these findings suggest that specific changes to the local environment in the gut are driven by a Ube3a maternal deletion, unaffected by varying housing conditions and are prominent and detectable across multiple small and large model species. These findings may begin to uncover the underlying mechanistic causes of GI disorders in AS patients and provide future therapeutic options for AS patients.IMPORTANCEAngelman syndrome (AS) associated gastrointestinal (GI) symptoms significantly impact quality of life in patients. Using AS models in mouse, rat, and pig, AS animals showed impaired colonization of the gut microbiota compared to wild type (healthy) control animals. Unique changes in AS microbiomes across all three animal models may be important in causing GI symptoms and may help to identify ways to treat these comorbidities in patients in the future.

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Section: Discussionmentioning

confidence: 86%

Unique features of the gut microbiome characterized in animal models of Angelman Syndrome

Beitnere

Vilanova-Cuevas

Christian

et al. 2022

Preprint

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“…Gut bacteria were largely overlooked until they were found to be closely related with various gut or gutrelated disorders, such as irritable bowel syndrome [36][37][38], infectious diarrhea [39], ulcerative colitis, colorectal cancer, liver diseases, and obesity related disorders [40,41]. In addition, gut bacteria can be utilized as a medication strategy [42][43][44][45][46], including fecal microbiota transplantation (FMT) [47][48][49][50][51][52]. Gut bacteria recently became an explosive topic, going through roughly three development stages: (1) Feces microbiota.…”

Section: Discussionmentioning

confidence: 99%

Liver microbiota in healthy rats: the hidden inhabitants of hepatocytes

Sun

Zhang

Xin

et al. 2022

Preprint

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The tumor and tissue microbiomes of human beings have recently been investigated. Gut permeability was known as a possible resource for the positive detection of tissue bacteria. Herein, we report that bacteria were detected in high abundance in the hepatocyte nucleus of healthy rats, and that they were shared with gut microbiota to an extent. We assessed male Sprague Dawley (SD) rats for the 16S ribosomal ribonucleic acid (rRNA) gene. After rats were sacrificed by blood drainage from the portal vein, we extracted total deoxyribonucleic acid (DNA) from their ileal and colonic contents and liver tissues. The V3–V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) and sequenced using an Illumina HiSeq 2500 platform. Sequences were assigned taxonomically by the SILVA database. We also detected bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in situ using immunofluorescence (IF) and western blotting and the 16S rRNA gene using fluorescent in situ hybridization (FISH). In the livers of six rats, we detected 54,867.50 ± 6450.03 effective tags of the 16S rRNA gene and clustered them into 1003 kinds of operational taxonomic units (OTUs; 805.67 ± 70.14, 729–893). Individuals showed conservation of bacterial richness, abundance, and evenness. LPS and the 16S rRNA gene were detected in the nuclei of hepatocytes. The main function composition of genomes of the annotated bacteria was correlated with metabolism (79.92 ± 0.24%). Gram negativity was about 1.6 times higher than gram positivity, and the aerobic and anaerobic phenotypes were nearly the same. Liver microbiota also showed high expression of mobile elements, biofilm formation, and stress tolerance, as well as potentially pathogenic phenotypes. Chemoheterotrophy, fermentation, and aerobic chemoheterotrophy were the main heterotrophic functions. Liver bacteria were shared with both the small and large intestines but showed significantly higher richness, evenness, and the β-diversity results showed that the liver microbiota exhibited significantly higher similarity than the small and large intestines (P < 0.05). The liver microbiota were hidden intracellular inhabitants in healthy rat livers and were shared with the gut microbiota.

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“…Bacterial metabolites can act as neurotransmitters. Thus, in addition to the classic diseases associated with alterations in the microbiota, the microbiota is also related to central nervous system conditions, ie, autism, anxiety, and depression [48][49][50].…”

Section: Human Gut Microbiotamentioning

confidence: 99%

Microbiome and Allergy: New Insights and Perspectives

Zubeldia-Varela¹,

Barker-Tejeda²,

Obeso³

et al. 2022

J Investig Allergol Clin Immunol

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The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies are increasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immune response to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skin microbiota and atopic dermatitis, and between gut microbiota and food allergy. The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics are the techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerably in recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased. Thus, more and more studies are proposing mechanisms for intervention in the microbiota. In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous, and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases. Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy.

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The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder

Cited by 52 publications

References 141 publications

Unique features of the gut microbiome characterized in animal models of Angelman Syndrome

Unique features of the gut microbiome characterized in animal models of Angelman Syndrome

Liver microbiota in healthy rats: the hidden inhabitants of hepatocytes

Microbiome and Allergy: New Insights and Perspectives

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