Laboratory of Alessio Fasano, MD
Overview
Dr. Alessio Fasano’s research is focused on the mechanisms of autoimmune and inflammatory diseases, particularly the role of intestinal permeability. In 2000 the Fasano’s lab discovered zonulin, a protein that regulates gut permeability, and its link to a variety of chronic inflammatory diseases, including autoimmune diseases, allergy, neurodevelopmental and neurodegenerative disorders, metabolic diseases, and cancer.
Key Areas of Research Focus
- Intestinal Barrier Function: Investigating how impaired tight junctions in the intestine lead to chronic inflammation and autoimmunity.
- Zonulin Pathway: Studying how the zonulin family peptides modulate gut permeability and influences disease onset.
- Celiac Disease & Non-Celiac Gluten Sensitivity: Leading research on the pathophysiology of celiac disease, including immune responses to gluten and the high prevalence of non-celiac gluten sensitivity.
- Gut Microbiome: Exploring how intestinal bacteria contribute to immune regulation and the progression of diseases.
- Autoimmune Diseases: Extending research from celiac disease to other diseases where permeability is a factor, such as Type 1 diabetes, multiple sclerosis, and autism.
Research Projects
CD-GEMM
The Celiac Disease Genomic, Environment, Microbiome, and Metabolomic (CD-GEMM) study is a multidisciplinary investigation aimed at identifying and validate specific microbiota and metabolomic profiles that can predict loss of tolerance in infants genetically at risk of autoimmunity in order to implement early preventive interventions to re-establish tolerance and ultimately prevent autoimmunity. We have focused our research effort on celiac disease (CD), a unique model of autoimmunity for which the triggering environmental factor (ingestion of gluten containing grains), a close genetic association with HLA genes (DQ2 or DQ8) and a highly specific humoral autoimmune response (autoantibodies to tissue transglutaminase) are known. To achieve our objective, we capitalize on our unique birth prospective cohort of infants at-risk of CD that have been followed for 10 years since birth. Our studies have subverted the previous notion that loss of gluten tolerance occurs at the time of its introduction in the child's diet; rather it can occur at any time in life as a consequence of other environmental stimuli. Our data also suggest that gut microbiome composition and consequent epigenetic reprogramming the gut epithelium controlling barrier function, immune response and cell turnover precede the onset of the disease and may contribute to switching from tolerance to immune response to gluten.
GEMMA
Autistic Spectrum Disorders (ASD) are a major concern for healthcare systems as they now affect 1 in 68 children around the world (a 35-fold increase since 1960) and carry larger societal costs than cancer, heart disease and stroke combined. The world is facing a pandemic of catastrophic proportions while the research community struggles to understand the mechanisms leading to the onset ASD. As of today, there are no proven biomarkers of ASD and diagnostic still relies entirely on behavioral evaluations. Worse, we know that infants born in a family with another member suffering from ASD have a 10x higher risk to develop ASD, but we do not have any possibility to administer a preventive treatment that could reduce this risk. Genome, Environment, Microbiome and Metabolomic in Autism (GEMMA) is the first project to combine a multi-omic approach with robust environmental data to identify and validate biomarker predictors of development in at-risk infants.
The project provides solid mechanistic evidence of the disease onset and progression in relation to dynamic changes in abnormal gut microbiota causing epigenetic modifications controlling gut barrier and immune functions, based on the in-depth evaluation of 360 infants at risk observed from birth.
The project will support novel personalized medicine approaches that attempt to modulate gut microbiota to re-establish/maintain immune homeostasis. The biomarkers identified in this project will contribute to a better understanding of the pathogenesis of ASD in at-risk children and the possibility to manipulate the microbiota through pre/pro/symbiotic administration +/- dietary changes for prevention and treatment, a complete paradigm shift in ASD pathogenesis and early intervention.
The identification of specific ASD metabolic phenotypes will also help to define biomarkers that can be used as diagnostic tools and patient stratification models for other conditions in which the interplay between genome, microbiome, and metabolic profile has been suspected or proved.
Finally, the project has collect biospecimens from a cohort of 360 infants as risk of ASD observed from birth, generating a unique biobank of 16,000+ blood, stool, urine and saliva samples that can be exploited in future multiomic studies, providing substantial value to the research community beyond project completion.