MetaBiom
Microbiome & Chronic Diseases

Evidence Based Medicine

Autism {40000120}

Record Keys
Definition:
Autism
Class:[  ]

Details
Other Terms:
Autism Spectrum Disorders, ASD
Authoring date:
2019-06-23

Links

Meta Information
ICD:[  ]
Category:
Psychiatric, Pediatric
MedDra ID:
10080683
MedDra Level:[  ]

Notes

- 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)

Shared Notes

  • [1.26] 
    - 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.
  • [1.27] 
    - 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.
  • [1.28] 
    - 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
  • [1.29] 
    - In autism patient Bacteroides, Bifidobacterium, Escherichia coli are reduces and Faecalibacterium, Lactobacillus are increased. The presence of Clostridium remains substantially unchanged
  • - 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.
  • - The reduction of Bifidobacterium also results in reduced levels of short-chain fatty acids (SCFAs), common in ASD children.
  • - 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
  • [1.30] 
    - 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
  • [1.25] 
    - 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

Common References