Intestinal and Blood-Brain Barrier Alterations Linked to Autism Spectrum Disorders

MedicalResearch.com Interview with:

Maria Rosaria Fiorentino, PhD

Dr. Maria Rosaria Fiorentino

Maria Rosaria Fiorentino, PhD
Assistant Professor at Harvard Medical School
Molecular Biologist at Mucosal Immunology and Biology Research Center
Massachusetts General Hospital East
Charlestown, MA 02129-4404

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Autism Spectrum Disorders (ASD) refers to complex neurodevelopmental disorders arising from the interaction of genes and environmental factors. There are no defined mechanisms explaining how environmental triggers can lead to these conditions. One hypothesis based on the gut-brain axis connection suggests that inappropriate antigens trafficking through an impaired intestinal barrier, followed by passage of these antigens through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to the disease.

Many Autism Spectrum Disorders children experience co-morbid medical conditions, including gastrointestinal (GI) dysfunctions whose underlying nature is poorly understood. Several clinical observations describe increased intestinal permeability in ASD with often conflicting findings. Permeability to neuroactive food antigens derived from the partial digestion of wheat (gliadorphins) and cow’s milk (casomorphins) has been reported in ASD. However, while evidence of a permeable gut barrier in ASD is increasingly reported, no information is available concerning a similar breach for the BBB. The BBB is a critical line of defense in the Central Nervous System, limiting the access of circulating solutes, macromolecules, and cells that could negatively impact neuronal activity. Dysfunctions of the BBB have been associated with numerous inflammatory neurologic disorders, such as stroke, epilepsy, multiple sclerosis, Parkinson’s and Alzheimer’s disease.

MedicalResearch.com:  What are the main findings?

Response: We found that Autism Spectrum Disorders subjects have an altered expression of components of the BBB associated with its integrity and function, as well as with neuroinflammation in postmortem brain tissues. Moreover, we have shown at a molecular level that 75% of ASD patients evaluated have gut barrier defects. Our findings suggest that increased gut and blood-brain-barrier permeability might be involved in the pathophysiology of ASD.

MedicalResearch.com: What should readers take away from this report?

Response: Our study is the first to explore mechanistically the molecular signature of defects in the gut epithelial barrier and the BBB in  Autism Spectrum Disorders. Our findings suggest there is a molecular mechanism linking the gut and brain that involves both the intestinal and the blood-brain barriers in the pathophysiology of ASD. Elucidating the molecular basis of gut and blood-brain barrier impairment in Autism Spectrum Disorders will be the first step toward the design of more targeted and effective therapies. If we can prevent alterations of the function of these barriers, we may be able to treat the GI symptoms and/or autism core symptoms in the ASD population.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study is part of a project aimed at testing our working hypothesis about the pathophysiology of ASD, which proposes that the combination of gut microbial dysbiosis, increased gut permeability, and the passage of non-self antigens and/or activated immune complexes through an impaired BBB interferes directly with the function of the Central Nervous System of ASD. Studies on animal models using fecal transplants from ASD children in which gut microbial dysbiosis and increased intestinal/blood-brain barrier permeability can be mechanistically linked to behavioral alterations typical of ASD would be helpful to fully understand the gut-brain crosstalk in neurodevelopmental disorders.

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Citation:
Maria Fiorentino, Anna Sapone, Stefania Senger, Stephanie S. Camhi, Sarah M. Kadzielski, Timothy M. Buie, Deanna L. Kelly, Nicola Cascella, Alessio Fasano. Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Molecular Autism, 2016; 7 (1) DOI: 10.1186/s13229-016-0110-z

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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