Gluten and Gut-Brain Axis

Gluten and Gut-Brain Axis:
Lesson Learned From
Autism And Schizophrenia
Alessio Fasano, M.D.
Mucosal Immunology and Biology Research Center
And Center for Celiac Research
Massachusetts General Hospital for Children
Pathogenesis Of
Neuropsychiatric Disorders
ASD
Genetics
Environment
+
=
Schizophrenia
Genes &
Environment?
Gentle concession by Dr. Li-Ching Lee, Johns Hopkins Blumberg School of Public Health
Summary of Linkage Findings Across Studies:
ASD
Summary of Linkage Findings Across Studies:
Schizophrenia
Why Environmental
Risk Factors ?
Increasing concerns
about environmental exposures
and neurodevelopment
in general
Provocative
data on mechanisms
by which environmental exposures
might cause
autism
Descriptive data on recent
rise in autism prevalence
Increased focus on
environmental exposure and
autism
Epidemiologic data on
environmental exposures and
autism
Lack of a definitive
genetic model for autism
•Many theories… Little to no evidence…
Gentle concession by Dr. Li-Ching Lee, Johns Hopkins Blumberg School of Public Health
The Epidemics Of
Neuropsychiatric Disorders
Which Factors are Driving
These Epidemics?
•Vaginal Delivery
•Proper Nutrition
•No infections
•No Antibiotic treatments
•C section
•Inappropriate Nutrition
•Multiple infections
•Antibiotic treatments
Microbiome
Composition
Probiotics
Balanced
Microbiome
Appropriate
GALT Maturation
Dysbiosis
+
Genetic
Predisposition
Tolerogenic Response to Food
Antigens - State of Health
+
Inappropriate
GALT Maturation
Pro-inflammatory Response to
Food Antigens - CID
The Gut-Brain Axis
Autism Epidemics:
Gluten and The Brain
Short Memory Loss
Chronic Headache
Anxiety
Depression
Schizophrenia?
Irritability
Autism?
Seizures
Ataxia
ADHD?
Figure 2. Comparison of levels of IgG and IgA antibody to gliadin in children with autism, their unaffected
siblings, and unrelated healthy controls.
Lau NM, Green PHR, Taylor AK, Hellberg D, et al. (2013) Markers of Celiac Disease and Gluten Sensitivity in Children with Autism.
PLoS ONE 8(6): e66155. doi:10.1371/journal.pone.0066155
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066155
Impact of the GF/CF Diet on anti Total anti-Gliadin and anti-Casein
Antibodies and on Total IgE and anti-Milk IgE In Autistic children(AU)
and Healthy Children (NC) and Impact of Gut Permeability on Milk IgE
De Magistris L. et al (2013)
How Zonulin, Gut Permeability and Inflammation
Are Relate to Schizophrenia and ASD?
Gliadorphins
Casomorphins
Activated
inflammatory cells
Gluten Causes Leaky Gut and Inflammation by
Releasing Zonulin
Anti-TTG6 Ab
TTG6
Brain Inflammation
CLDN4
Acknowledgments
NIH DK078699
NIH DK048373
The MIBRC Crew