Microbiome & Chronic Diseases

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Disease ⇒ Autism {40000120}

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Other Terms:
Autism Spectrum Disorders, ASD


Meta Information

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MedDra Level:[  ]
ICD:[  ]
Psychiatry, Pediatric
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Mechanism:[  ]


- Twenty-seven of their 313 metabolites in faeces and serum were also different, and of the 313, two – 5-aminovaleric acid (5AV) and taurine – were also present in lower quantities. These two molecules are neurotransmitter agonists: their molecular structures resemble that of the GABA and glycine neurotransmitters, and they interfere with the latter’s functions.” As it happens, both GABA and glycine, help the brain develop normally.
And when the scientists injected the mice with 5AV and taurine, the rodents developed ASD-like symptoms. Ergo, bacteria probably interfere with brain functions using these molecules. (1)

- Members of the C. histolyticum group are recognized toxin-producers and may contribute towards gut dysfunction, with their metabolic products also exerting systemic effects.
- Strategies to reduce clostridial population levels harboured by ASD patients or to improve their gut microflora profile through dietary modulation may help to alleviate gut disorders common in such patients. (3)

- L. reuteri produces a metabolite that activates the vagus nerve to promote oxytocin, the cuddle hormone.This hormone then turns on the brain reward center for social behavior. Impeding the message at any point along this relay from bacteria to metabolite to vagus nerve to oxytocin receptors impairs the animals sociability (4)

- Blood of mice with autism symptoms had levels of a chemical called 4-ethylphenylsulphate (4EPS) that were 46 times higher than that of the control group. This substance is structurally similar to a chemical called para-cresol that is elevated in people with autism .
- When the researchers injected 4EPS into wild-type mice, they started behaving like the untreated autistic mice - obsessively repeating some behaviours and squeaking differently when greeting other mice. (5)

- ASD mice were fed with Bacteroides fragilis, a gut microbe with positive effects on the immune system, the abundance of 34% of these metabolites changed back, gut barrier integrity was improved, the gut-microbiome was restored to a non-ASD state, and ASD-related behavioral abnormalities were ameliorated. In addition, a 46-fold increase of 4-ethylphenylsulfate (4-EPS) in the serum of MIA offspring returned to normal levels.
-A second metabolite elevated in the MIA serum, and normalized by treatment with B. fragilis, was indolepyruvate. Indolepyruvate is generated by microbial tryptophan catabolism and is related to indolyl-3-acryloylglycine, another human autism marker. Indolepyruvate elevation could be linked to increased serum levels of serotonin, yet another human autism biomarker.
- Application of the B. fragilis probiotic, increased many other metabolites including N-acetylserine, which the authors hypothesize may provide protection against some ASD symptoms. (6)

- Bifidobacterium, Blautia, Dialister, Prevotella, Veillonella, and Turicibacter were consistently decreased, while Lactobacillus, Bacteroides, Desulfovibrio, and Clostridium were increased in patients with ASD relative to HCs in certain studies. (7)

- ASD patients reported a decrease in Bifidobacterium and increase in Faecalibacterium and Clostridium genera in ASD patients.
- In individuals with ASD > fecal metabolome > ncrease in p-cresol, a bacterial metabolite derived from tyrosine.

Shared Reference Notes

  • [1.1
    - There is a high coincidence of gastrointestinal (GI) symptoms and compositional changes within the gut microbiome in individuals with ASD. - The degree of GI symptomatology, including constipation and diarrhea, may correlate with the severity of ASD. - Microbiome-induced inflammation’s potential to alter the blood-brain barrier (BBB) permeability. - The same factors affecting gut permeability also affect the permeability of the BBB. - The translocation of pro-inflammatory molecules across the intestinal barrier causes a low-grade systemic inflammatory response, which can alter the BBB’s permeability
  • [1.2
    - Specifically, Bacteroidetes, Bacteroides, and Parabacteroides were decreased in oASD mice, with an increase in Akkermansia, Sutterella, and Lachnospiraceae, as has been reported in humans. - Both the Bacteroides spp. (b20cd_Bacteroides) and P. merdae (4ae7e_Parabacteroides) correlated with reduced repetitive behavior and increased social behavior. - E. tayi (02b40_Lachnospiraceae) showed the opposite effects, as it correlated with increased repetitive behavior and social interaction deficits - P. merdae, were more abundant in ASD individuals from human.
  • [1.3
    - In autism patient Bacteroides, Bifidobacterium, Escherichia coli are reduces and Faecalibacterium, Lactobacillus are increased. The presence of Clostridium remains substantially unchanged
  • [#Antibiotic Therapy] - Autism patients who have had their intestinal microbiota remodeled through the administration of antibiotics or bacterial transfer therapy in the intestine, presented with attenuated symptoms of ASD
  • [#Short Chain Fatty Acid] - The reduction of #Bifidobacterium also results in reduced levels of short-chain fatty acids (SCFAs), common in ASD children.
  • - Increase in #Faecalibacterium in ASD children is responsible for the progression of inflammatory processes, with increased levels of type I interferon, and the alteration of the intestinal barrier.
  • [1.4] [#Limosilactobacillus (Lactobacillus) reuteri
    - Treatment with L. reuteri selectively rescues social deficits in genetic, environmental, and idiopathic ASD models. - The effects of L. reuteri on social behavior are not mediated by restoring the composition of the host gut microbiome, which is altered in all of these ASD models. - L. reuteri acts in a vagus nerve-dependent manner and rescues social interaction-induced synaptic plasticity in the ventral tegmental area of ASD mice, but not in oxytocin receptor-deficient mice
  • [1.5] [#Limosilactobacillus (Lactobacillus) reuteri
    - Host genetics and microbiota differentially regulate behaviors in an ASD mouse model - Microbe therapy (L. reuteri) rescues social deficits in ASD mouse model but not hyperactivity - Microbe-induced metabolite tetrahydrobiopterin (BH4) selectively rescues social deficits in ASD mouse model - L. reuteri and tetrahydrobiopterin (BH4) improves in ASD mouse model social-reward-mediated synaptic transmission
  • [1.6] [#Clostridioides difficile
    - Autism incidence has been found to be higher in the C. difficile diseased population.
  • [1.7
    - The microbial metabolite #p-cresol induces selectively ASD core behavioral symptoms in mice. - Social behavior deficits induced by #p-cresol are dependant on changes in microbiota composition.
  • [1.8] [#Folic acid
    - There is an increased frequency of serum auto-antibodies against folate receptor alpha (FRAA) in autism spectrum disorder children.
  • [1.9] [#Indolyl-3-acryloylglycine
  • [#Indolepyruvate
  • [1.11] [#p-cresol
  • [1.12
  • [1.13
    - #Beta-glucan food supplement > significant decrease in the Childhood Autism Rating Scale score in all of the children of the Nichi Glucan Gr.2 compared with the control. Plasma levels of #Alpha-synuclein were significantly higher in (Nichi Glucan) than in the control group.
  • [1.14] [#Alpha-synuclein, #Amyloid, #Beta-glucan, #Curli] [#Nichi Glucan
  • [1.15
    - children with autism, SCFA levels were differentially altered, with an increase in #Propionate and #Acetate and a decrease in #Butyrate levels. - rats fed with #Propionate exhibited phenotypic features similar to those of autism.
  • [1.16
    - Treatment with #Vitamin B12 in rats with experimental autism improved impaired markers of this neurologic condition
  • [1.17
    - Fecal microbiota transplant (FMT) via gavage from autistic children donors to mice, led to the colonization of ASD-like microbiota and autistic behaviors compared to the offspring of pregnant females exposed to #Valproic acid (VPA). - Such variations seemed to be tightly associated with increased populations of Tenericutes plus a notable reduction (p < 0.001) of Actinobacteria and Candidatus S. in the gastrointestinal region of FMT mice as compared to controls.
  • [1.18
    - up-regulation was found for some metaproteins associated with #Clostridia and with carbohydrate metabolism (glyceraldehyde-3-phosphate and glutamate dehydrogenases), while down-regulation was observed for others associated with #Bacteroidia
  • [1.19] [#Inflamatory bowel disease] [#Sutterella wadsworthensis
    - Sutterella, a Gram-negative genus from Proteobacteria, has been associated with various diseases including autism and inflammatory bowel disease (IBD)
  • - The depletion of #Bifidobacterium species has been reported widely in ASD. - #Bifidobacteria are SCFA producers, and “psychobiotics” , and they modulate the gut–brain signals via γ-aminobutyric acid (GABA) and #Glutamate metabolism. - #Bifidobacterium have been reported to improve behavior and prevent #Depression-like behaviors in mice.
  • - A higher relative abundance of #Alistipes species has been reported in children with autism, pervasive developmental disorder not otherwise specified (PDD-NOS) , and depression. - #Alistipes may disrupt the gut–brain axis by decreasing #Serotonin (indole-positive organism) and impair cognition by producing #Propionic acid in rats.
  • - lower levels of #Prevotella and #Bifidobacterium may lead to reduced levels of #Folate production due to diminished #Folate-dependent remethylation in ASD
  • - lower or depleted levels of #Prevotella in ASD compared to TD in fecal and oral microbiota. - Many gut #Prevotella species are fiber-consuming bacteria.
  • [1.21] [#Cancer
    - #Lachnoclostridium depleted in other psychiatric disorders including #Schizophrenia and autism and in patients with gastrointestinal tract neoplasms.
  • [1.22
    - L. reuteri produces a metabolite that activates the vagus nerve to promote oxytocin, the cuddle hormone.This hormone then turns on the brain reward center for social behavior. Impeding the message at any point along this relay from bacteria to metabolite to vagus nerve to oxytocin receptors impairs the animals sociability.
  • [1.23

References Notes

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Common References