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The Microbiome and the Microchondria
Talking Points The enteric (gut) microbiome has an important influence in
- n health and disease states in humans.
The Enteric (Gut) Microbiome Modulates Mitochondrial Function - - PowerPoint PPT Presentation
The Enteric (Gut) Microbiome Modulates Mitochondrial Function - - PowerPoint PPT Presentation
The Enteric (Gut) Microbiome Modulates Mitochondrial Function Richard E. Frye, M.D., Ph.D. Child and Behavioral Neurologist Arkansas Childrens Hospital University of Arkansas for Medical Sciences The Microbiome and the Microchondria
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The Microbiome and the Microchondria
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Bacteria use a complex communication network to thrive in an environment
The Microbiome and Neurodevelopmental Disorders
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The microbiota induces host immune tolerance
The Microbiome and Neurodevelopmental Disorders
Segmented Filamoentous Bacteria Gut assocatied lymphoid tissue
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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Autism Spectrum Disorder and the Microbiome
The Microbiome and Neurodevelopmental Disorders
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Propionic Acid Model of Autism: Animal Models
The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
CA1 & CA2 CA3/Dentate Hippocampus Total 10000 20000 30000 40000 50000 60000 70000
* *
Mean Area (µm
2 )
Saline PPA500
Hippocampus - GFAP *
Propionate increases GFAP, Marker of Reactive Astrocytes and immunoreactivity in hippocampus Neuropathology Quantification
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The Microbiome and Neurodevelopmental Disorders
CD68 marker of Microglia
Control (PBS) PPA
PPA increases activated microglia (neuroinflammation)
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The Microbiome and Neurodevelopmental Disorders
Interleukin 6 PBS PPA White Matter Hippocampus
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The Microbiome and Neurodevelopmental Disorders
PBS Vehicle High Dose PPA PPA causes increase anti Nitro-tyrosine immunoreactivity in hippocampal formation, a measure of oxidative stress Nitrotyrosine Immunoreactivity, a measure of oxidative stress
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Developmental delay in pups
Eye Opening
Post-natal day
12 13 14 15 16
# eyes open
1 2
2-VEH (38) LPS (42) 5-VEH (43) PPA (47)
* **
^^
*** Developmental milestones are delayed in pups prenatally exposed to PPA and LPS (ie. pinna detachment, incisor eruption). (PPA similar to valproic acid- mitochondrial function/gene expression)
** p < .01, *** p < .001: PPA ^^ p < .01: LPS
The Microbiome and Neurodevelopmental Disorders
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Acoustic startle response: Prenatal PPA and LPS produce hyper-sensitivity to stimulus
Sex Male Female
Average startle response
200 400 600 800 1000
2-VEH LPS 5-VEH PPA
** ** ** **
n = 14-15 per group ** p < .01: LPS, PPA Males higher than females, regardless of treatment.
Other anxiety-like behaviour also present in PPA and LPS animals. The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
Propionic Acid Model of Autism: Parallels of Children with Autism
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- 213 ASD patients screened with acyl-carnitine biomarkers
- 74 (35%) with >=3 fasting acyl-carnitine elevations
- Acyl-carnitine abnormalities were confirmed in 48%
- Corrected prevalence of 17% of ASD children screened.
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Autistic Children Rodents
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Rodents ASD Children
The Microbiome and Neurodevelopmental Disorders
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Decreased Complex I Activity
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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GI-After = GI Symptoms started after the onset of Autism symptoms GI-Before/Same = GI Symptoms started before or at the same time as Autism symptoms
The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
Early Immune Activation Model of Autism: Animal Model and Probiotic Treatment
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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Microbiota Transfer Therapy (MTT)
The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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The Microbiome and Neurodevelopmental Disorders
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