About

Dr. Alessio Fasano is a Professor of Pediatrics at Harvard Medical School and a Professor of Nutrition at Harvard T.H. Chan School of Public Health. He serves as the Chief of the Division of Pediatric Gastroenterology and Nutrition at Massachusetts General Hospital, where he also holds the W. Allan Walker Chair of Pediatric Gastroenterology and Nutrition. Additionally, Dr. Fasano is the Director of the Center for Celiac Research and Treatment and the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital in Boston, Massachusetts. His translational science focuses on the role of impaired intestinal barrier function in the pathogenesis of autoimmune and inflammatory diseases, including celiac disease, autism, and type 1 diabetes. As an expert in celiac disease, intestinal permeability, and autoimmune disorders, Dr. Fasano is widely sought after for his research and clinical expertise in these areas.

Research topics

• Medicine
• Virology
• Internal medicine
• Immunology
• Biology
• Obstetrics
• Endocrinology
• Genetics

Selected publications

• Profiling the Athletes’ Gut Microbiome: A Critical Methodological Perspective on 16S Metabarcoding and Shotgun Metagenomics

  Biology · 2026-04-10

  articleOpen accessSenior author

  The growing interest in the role of the gut microbiome in athletic performance has led to the application of various sequencing technologies in this field. This review critically examines the sequencing methodologies used in microbiome studies on physical performance and sport, comparing their advantages, limitations, and applicability. In particular, the focus is on 16S metabarcoding and shotgun metagenomics, evaluating how these methodological approaches influence the interpretation of results in sports contexts. Close attention is directed toward technical challenges, methodological biases, and future perspectives, including emerging technologies and multi-omics approaches. This review aims to bridge the gap between methodological rigor and sports-specific applicability, providing evidence-based methodological guidance to support researchers in designing robust athlete microbiome studies and translating sequencing-derived findings into concrete applications for performance and sports health.

  PublisherOA PDFDOI

• Elevated Microbially-Derived Metabolites in Autism: A Possible Diagnostic Screening Test for a Distinct ASD Phenotype

  Research Square · 2025-10-02 · 1 citations

  preprintOpen access
  PublisherOA PDFDOI

• Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide

  Science Translational Medicine · 2025-07-30 · 2 citations

  articleSenior author

  Multisystem inflammatory syndrome (MIS) is a severe disease that occurs weeks to months after acute infection with SARS-CoV-2, often occurring in children (MISC). Symptoms include high fever, rash, nausea, diarrhea, and abdominal pain. Children with MISC can develop cardiovascular injury including ventricular failure, coronary artery aneurysms, or shock. Current treatment strategies for these postacute sequelae of COVID-19 primarily target the hyperinflammatory response. However, a potential role for viral spike protein translocated via zonulin-mediated trafficking from gastrointestinal reservoirs of SARS-CoV-2 into the circulation has been suggested. Here, we report results from a phase 2a randomized, double-blind, placebo-controlled clinical trial testing the zonulin antagonist larazotide in 12 children with MISC with a median age of 5.7 years. Children were enrolled during hospitalization for acute MISC and were treated with adjuvant larazotide therapy four times daily for 3 weeks. Patients were monitored for 24 weeks for safety follow-up. No larazotide-related adverse events were reported. The concentration of SARS-CoV-2 spike protein antigen in blood samples correlated with inflammatory markers, including interferon-γ (IFN-γ) ( P = 0.004) and interleukin-6 (IL-6) ( P < 0.0001), and with gastrointestinal symptoms as assessed by the PedsQL GI symptom score ( P = 0.003). Children treated with larazotide displayed faster resolution of gastrointestinal symptoms, faster clearance of spike antigen, and a faster return to usual activities. Our findings suggest that larazotide treatment may be safe in children and may improve resolution of symptoms when used as an adjuvant therapy for MISC.

  PublisherDOI

• Biomarkers of intestinal permeability in major psychiatric disorders: Distinct biological roles call for a more nuanced application

  Progress in Neuro-Psychopharmacology and Biological Psychiatry · 2025-05-26 · 7 citations

  reviewOpen access

  BACKGROUND: Zonulin, lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14) are frequently used as proxy biomarkers of intestinal permeability in studies involving patients with psychiatric disorders. Although often used interchangeably, these biomarkers reflect distinct biological processes. OBJECTIVE: This review integrates evidence from basic research on the mechanisms of action of zonulin, LBP, and sCD14 with findings from studies on major depressive disorder, bipolar disorder, and schizophrenia spectrum disorders, aiming to refine their application in gut-brain axis research. FINDINGS: Zonulin is consistently elevated in schizophrenia spectrum disorders and appears most closely linked to gut barrier integrity and systemic immune activation. LBP is consistently elevated in major depressive disorder and may reflect underlying alterations in gut permeability, metabolic status, and psychological stress. sCD14 has been primarily studied in schizophrenia spectrum disorders, where findings are more heterogeneous, and is thought to reflect generalized monocyte activation. These biomarkers were largely unrelated to clinical symptom severity, with the exception of sCD14, which showed associations with positive symptoms, aggression, and the number of manic episodes. CONCLUSIONS: Zonulin, LBP, and sCD14 each capture unique aspects of gut and immune system function. Their interchangeable use risks misinterpretation. A more nuanced, context-dependent application-tailored to specific research questions or intervention targets-is essential for advancing gut-brain axis research in psychiatry.

  PublisherDOI

• Characterizing zonulin and par2 Expression in Zonulin Transgenic and Zonulin Inhibition Mouse Models of Motility and Inflammation

  International Journal of Molecular Sciences · 2025-07-02

  articleOpen accessSenior authorCorresponding

  We aimed to examine the effect of zonulin and zonulin inhibition on gastrointestinal (GI) motility and the mRNA expression of zonulin and the protease-activated receptor 2 (par2), the primary receptor for zonulin, under conditions of inflammation by lipopolysaccharide (LPS) injection. The experimental models included zonulin transgenic mice (ztm), par2 knockout ztm (ztm-par2 −/−), ztm exposed to the zonulin inhibitor AT1001 (ztm-AT1001), and wildtype mouse controls. GI transit was measured by fluorescein isothiocyanate-dextran and mRNA expression by real-time quantitative polymerase chain reaction in whole, and in epithelial and non-epithelial tissues of all GI segments. There were no differences in the GI transit between mouse groups at baseline. After the LPS injection, ztm mice had an attenuated slowing of the GI transit compared to wildtype mice. The zonulin-inhibited mice had motility patterns similar to wildtype mice. zonulin upregulation was noted in GI segments of the ztm, ztm-par2 −/−, and ztm-AT1001 after the LPS injection. Differences in motility patterns between ztm and zonulin inhibition models despite zonulin expression in GI segments of all mouse groups supports that PAR2 is key for zonulin’s effect on motility under conditions of inflammation. However, the findings from the epithelial and non-epithelial compartments suggest that the pathway of activity is complex and likely indirect.

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• Investigating intestinal epithelium metabolic dysfunction in celiac disease using personalized genome-scale models

  BMC Medicine · 2025-02-21 · 4 citations

  articleOpen access

  BACKGROUND: Celiac disease (CeD) is an autoimmune condition characterized by an aberrant immune response triggered by the ingestion of gluten, which damages epithelial cells lining the small intestine. Small intestinal epithelial cells (sIECs) play key roles in the enzymatic digestion and absorption of nutrients, maintaining gut barrier integrity, and regulating immune response. Chronic inflammation and tissue damage associated with CeD disrupt the intricate network of metabolic processes in sIECs that support these functions, impairing their ability to perform their essential roles. However, the specific disrupted metabolic processes underlying sIECs dysfunction in CeD remain largely undefined. METHODS: To address this knowledge gap, personalized, sex-specific genome-scale models of sIECs metabolism were constructed using transcriptional data from intestinal biopsies of 42 subjects with active CeD, CeD in remission (on a gluten-free diet), and non-CeD controls. These models were computationally simulated under relevant dietary conditions for each group of subjects to assess the activity of several metabolic tasks essential for sIECs function and to profile metabolite secretion into the bloodstream and intestinal lumen. RESULTS: Significant alterations in the activity of 28 essential metabolic tasks were observed in active CeD and remission CeD, impacting critical processes integral to sIECs function such as oxidative stress regulation, nucleotide synthesis and DNA repair, energy production, and polyamine and amino acid metabolism. Additionally, altered secretion profiles of several metabolites, encompassing amino acids, vitamins, polyamines, lipids, and fatty acids, into the bloodstream were detected in active CeD and remission CeD patients. These findings were partially supported by comparisons with independent external datasets and further corroborated through extensive review of existing literature. Furthermore, a drug target analysis was performed, identifying 22 FDA-approved drugs that target genes encoding impaired sIECs metabolic functions in CeD, potentially helping to restore their normal activity. CONCLUSIONS: This study unveils new insights into the metabolic reprogramming of sIECs in CeD, highlighting specific dysregulated metabolic processes that compromise cellular functions essential for gut health. These findings offer a foundation for developing therapeutic interventions targeting impaired metabolic processes in CeD.

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• Dynamic stability of gut microbiota in elite volleyball athletes: microbial adaptations during training, competition and recovery

  Frontiers in Sports and Active Living · 2025-09-03 · 3 citations

  articleOpen access

  Introduction To examine how different weekly training and competition schedules influence gut microbiota composition in elite volleyball players, investigating the relationship between training and competition demands, recovery periods and microbial dynamics to identify potential biomarkers for training load and recovery status assessment. Methods Seven elite athletes from the Italian Men's SuperLega Championship (age: 26.5 ± 4.5 years; weight: 96 ± 11 kg; height: 200 ± 0.1 cm; BMI: 24 ± 1.9) were monitored at four timepoints over eight weeks Regular Season periods (T0, T1), Rest Period (T2) and International Tournament Period (T3). Faecal samples underwent 16S rRNA sequencing analysis, with concurrent Mediterranean Diet adherence and Stool Consistency assessments. Repeated measures ANOVA and one-way ANOVA were performed to evaluate microbial abundance changes. Results 16S rRNA sequencing revealed Firmicutes predominance (41.22–76.03%), followed by Actinobacteria (9.66–54.45%) and Bacteroidetes (0.73–26.56%). The Firmicutes/Bacteroidetes ratio fluctuated in response to training intensity and competition 6:1 during T0 and T1, decreasing to 3:1 during T2 and returning to 5:1 during T3. Dominant bacterial families included Ruminococcaceae (26.97–28.3%), Bifidobacteriaceae (17.46–22.92%) and Lachnospiraceae (9.66–12.61%). Significant enrichment of Rikenellaceae abundance occurred during Rest Periods ( p < 0.05). α -Diversity remained stable despite individual variation. Mediterranean diet adherence declined during Regular Season Periods (T0: 6.3 ± 1.5, T1: 5.5 ± 0.8), while stool consistency gradually improved. Discussion Despite overall stability, elite athletes gut microbiota adapted to volleyball varying training demands primarily via Firmicutes/Bacteroidetes ratio modulations and Rikenellaceae enrichment during Recovery Periods. These microbial alterations represent potential biomarkers for assessing training load and recovery status. Additional investigation is necessary to elucidate how these microbial dynamics influence athletic performance outcomes.

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• Precision medicine for depression: Improving treatment response and remission

  Asian Journal of Psychiatry · 2025-06-21 · 8 citations

  reviewOpen accessSenior author

  This review synthesises current knowledge to improve understanding of the pathophysiology of major depressive disorder (MDD) and optimise diagnostic, therapeutic and prognostic approaches. It examines the interplay between genetic, epigenetic, inflammatory, neurotransmitter and gut microbiome factors, together with environmental stressors and different clinical symptom presentations, in shaping MDD presentation and treatment response. Studies have revealed potential biomarkers predictive of treatment response, allowing differentiation of MDD subtypes and facilitating remission monitoring. While studies have identified potential biomarkers predictive of treatment response and enabling MDD subtype differentiation, significant challenges remain in achieving fully optimized therapeutic efficacy and widespread remission. A holistic, data-driven approach is key to addressing the complex aetiology of MDD, ultimately improving outcomes for patients and reducing the substantial burden of this prevalent disorder. • This review explores the complex interplay of biological, environmental, and clinical factors in Major Depressive Disorder, focusing on the potential of multi-omics approaches to improve diagnosis, treatment, and remission monitoring. By integrating genomic, transcriptomic, metabolomic, and metagenomic data, researchers aim to identify reliable biomarkers, predict treatment response, and personalize therapeutic strategies. The review highlights the significant role of inflammation, gut microbiota, and genetic factors in MDD pathophysiology and underscores the need for a holistic, multi-faceted approach to address this challenging disorder.

  PublisherDOI

• 340: EXPOSOMIC INSIGHTS INTO ENVIRONMENTAL FACTORS INFLUENCING CELIAC DISEASE RISK

  Gastroenterology · 2025-05-01

  article
  PublisherDOI

• Elevation of tTG-IgA Antibodies in a Prospective Cohort of Children at Risk of Celiac Disease: Insights From the CDGEMM Cohort

  The American Journal of Gastroenterology · 2025-09-29 · 1 citations

  articleOpen access

  Celiac disease (CeD) is a common immune-mediated condition that occurs in genetically predisposed individuals. In this study, we examined the trajectory of tissue transglutaminase IgA (tTG-IgA) antibodies in a prospective longitudinal cohort of over 500 children at risk of developing CeD due to having a first-degree relative with CeD. We identified 34 subjects from our cohort and examined tTG-IgA titers at seroconversion and 6 months before tTG-IgA seroconversion. We found that all subjects had normal tTG-IgA 6 months before seroconversion. Thus, we conclude that tTG-IgA elevation in subjects with CeD is a sudden event and its trajectory cannot be used as a marker to predict seroconversion in this population.

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Recent grants

• NIH Grant U19AI090873

  NIH · $14.6M · 2016

• NIH Grant R21DK078699

  NIH · $413k · 2011

• NIH Grant U19AI082655

  NIH · $55.7M · 2020

• Boston Area Nutrition Obesity Research Center (NORC)

  NIH · $13.2M · 1997–2027

• NIH Grant R01DK048373

  NIH · $5.1M · 2017

Frequent coauthors

• Maureen M. Leonard

  Massachusetts General Hospital

  176 shared

• Gloria Serena

  SQZ Biotech (United States)

  163 shared

• Andrea G. Edlow

  Massachusetts General Hospital

  147 shared

• Carlo Catassi

  Marche Polytechnic University

  143 shared

• Lael M. Yonker

  Harvard University

  138 shared

• Victoria Kenyon

  Beth Israel Deaconess Medical Center

  111 shared

• Anna Sapone

  Pfizer (United States)

  86 shared

• Stefano Guandalini

  University of Chicago

  85 shared

Labs

• Massachusetts General HospitalPI