Larazotide Acetate
Also known as: AT-1001, INN-202, Tight Junction Regulator Peptide
Larazotide acetate is an 8-amino acid peptide (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) derived from Zonula Occludens Toxin (ZOT) of Vibrio cholerae. It paradoxically acts as a ZOT antagonist to close tight junctions and reduce intestinal permeability ('leaky gut'). It is the most advanced clinical compound targeting gut permeability directly.
Half-Life
Local gut action; minimal systemic exposure
Route
Oral
Category
Recovery & Repair
Studies
50 references
Key Benefits
- Directly reduces intestinal tight junction permeability
- Clinical efficacy in celiac disease (Phase 3 trials)
- Reduces systemic inflammation from gut permeability
- Targets root cause of leaky gut (Zonulin pathway)
- Local gut action without systemic absorption
- Potential application in IBS, IBD, autoimmune conditions
Mechanism of Action
Larazotide binds to the ZOT receptor (which normally opens tight junctions) and blocks its action, thereby maintaining or restoring tight junction integrity. It specifically targets the Zonulin pathway — the same pathway activated by gliadin in celiac disease and dysbiosis in IBD. It acts locally in the gut lumen without systemic absorption.
Dosing Protocols
Celiac Disease (Clinical Trial Dose)
- Dose
- 0.5-2 mg
- Frequency
- 3x daily
- Timing
- With meals
- Cycle
- 12-24 weeks
Phase 3 trial dose; reduces celiac symptom severity; most effective at 0.5 mg TID
Leaky Gut / General Use
- Dose
- 500 mcg - 1 mg
- Frequency
- 3x daily
- Timing
- With meals
- Cycle
- 8-16 weeks
Off-label use for general gut permeability reduction; stack with BPC-157 and KPV
Calculate your draw volume
Enter your vial size and BAC water to get exact injection volumes
Side Effects
- Headache (mild, dose-dependent)
- Nausea (rare)
- Well-tolerated overall in clinical trials
Storage
Stable at room temperature; follow manufacturer specifications for pharmaceutical formulations.
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Clinical Research
- 1.Larazotide Acetate Protects the Intestinal Mucosal Barrier from Anoxia/Reoxygenation Injury via Various Cellular Mechanisms
Kim J, Madan JP, Laumas S, Krishnan BR, Jin Y · Biomedicines · 2025PubMed Verified
- 2.Is There a Future Without Gluten Restrictions for Celiac Patients? Update on Current Treatments
Girbal-González M, Pérez-Cano FJ · Nutrients · 2025ReviewPubMed Verified
- 3.Antibacterial hyaluronic acid hydrogel with sustained release of larazotide as effective colitis treatment
Yu F, Chen Y, Ouyang S, Tong B, Jiang Z, Wang J et al. · Journal of controlled release : official journal of the Controlled Release Society · 2025PubMed Verified
- 4.Coeliac disease and the intestinal barrier: mechanisms of disruption and strategies for restoration
Damianos JA, Bledsoe A, Camilleri M, Murray JA · Gut · 2025ReviewPubMed Verified
- 5.Preventive effects of Larazotide acetate (AT-1001) on non-alcoholic fatty liver diseases (NAFLD) in a mouse model
Huang YC, Chiang Chiau JS, Cheng ML, Lee HC, Chan WT, Chang SW et al. · Pediatrics and neonatology · 2026PubMed Verified
- 6.New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review
Dipasquale V, Romano C · Healthcare (Basel, Switzerland) · 2025ReviewPubMed Verified
- 7.Elucidating the Significance of Zonulin in the Pathogenesis of Chronic Inflammatory Disorders: Emphasis on Intestinal Barrier Function and Tight Junction Regulation
Mohammadi-Kordkhayli M, Mousavi MJ, Camara-Lemarroy CR, Noorbakhsh F, Saboor-Yaraghi AA · Current medicinal chemistry · 2025ReviewPubMed Verified
- 8.Oral administration of RDP58 ameliorated DSS-induced colitis in intestinal microbiota dependent manner
Zheng D, Ke X, Cai H, Yan C, Chen Y, Sun J et al. · International immunopharmacology · 2024PubMed Verified
- 9.Celiac disease: Hope for new treatments beyond a gluten-free diet
D'heedene M, Vanuytsel T, Wauters L · Clinical nutrition (Edinburgh, Scotland) · 2024Meta-AnalysisPubMed Verified
- 10.Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats
Karahan D, Harputluoglu MMM, Gul M, Gunduz A, Ozyalin F, İnceoğlu F et al. · Digestive diseases and sciences · 2024PubMed Verified
- 11.Bromelain and ficin proteolytic effects on gliadin cytotoxicity and expression of genes involved in cell-tight junctions in Caco-2 cells
Mousavi Maleki MS, Aghamirza Moghim Ali Abadi H, Vaziri B, Shabani AA, Ghavami G, Madanchi H et al. · Amino acids · 2023PubMed Verified
- 12.Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions
Veres-Székely A, Szász C, Pap D, Szebeni B, Bokrossy P, Vannay Á · International journal of molecular sciences · 2023ReviewPubMed Verified
- 13.Targeting endothelial tight junctions to predict and protect thoracic aortic aneurysm and dissection
Yang X, Xu C, Yao F, Ding Q, Liu H, Luo C et al. · European heart journal · 2023PubMed Verified
- 14.Sex-dependent Lupus Blautia (Ruminococcus) gnavus strain induction of zonulin-mediated intestinal permeability and autoimmunity
Silverman GJ, Deng J, Azzouz DF · Frontiers in immunology · 2022PubMed Verified
- 15.Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic
Ailioaie LM, Ailioaie C, Litscher G, Chiran DA · International journal of molecular sciences · 2022ReviewPubMed Verified
- 16.Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats
Caliskan AR, Gul M, Yılmaz I, Otlu B, Uremis N, Uremis MM et al. · Human & experimental toxicology · 2021PubMed Verified
- 17.Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation
Di Micco S, Musella S, Sala M, Scala MC, Andrei G, Snoeck R et al. · International journal of molecular sciences · 2021PubMed Verified
- 18.Current pharmacological approaches and potential future therapies for Celiac disease
Kulkarni A, Patel S, Khanna D, Parmar MS · European journal of pharmacology · 2021ReviewPubMed Verified
- 19.Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials
Hoilat GJ, Altowairqi AK, Ayas MF, Alhaddab NT, Alnujaidi RA, Alharbi HA et al. · Clinics and research in hepatology and gastroenterology · 2022Meta-AnalysisPubMed Verified
- 20.Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier
Yonker LM, Gilboa T, Ogata AF, Senussi Y, Lazarovits R, Boribong BP et al. · The Journal of clinical investigation · 2021PubMed Verified
- 21.Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions
Slifer ZM, Hernandez L, Pridgen TA, Carlson AR, Messenger KM, Madan J et al. · PloS one · 2021PubMed Verified
- 22.Larazotide acetate: a pharmacological peptide approach to tight junction regulation
Slifer ZM, Krishnan BR, Madan J, Blikslager AT · American journal of physiology. Gastrointestinal and liver physiology · 2021ReviewPubMed Verified
- 23.In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model
Enomoto H, Yeatts J, Carbajal L, Krishnan BR, Madan JP, Laumas S et al. · PloS one · 2021PubMed Verified
- 24.Tight junction regulation in celiac disease: role of larazotide acetate
Armandi A, Pellicano R, Caviglia GP · Minerva gastroenterology · 2022PubMed Verified
- 25.The tight junction and the epithelial barrier in coeliac disease
Jauregi-Miguel A · International review of cell and molecular biology · 2021ReviewPubMed Verified
- 26.In silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate
Di Micco S, Musella S, Scala MC, Sala M, Campiglia P, Bifulco G et al. · Frontiers in chemistry · 2020PubMed Verified
- 27.Lack of relationship of AT1001 to zonulin and prehaptoglobin-2: clinical implications
Sollid LM, Koning F · Gut · 2021PubMed Verified
- 28.The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases
Troisi J, Venutolo G, Terracciano C, Carri MD, Di Micco S, Landolfi A et al. · Current medicinal chemistry · 2021ReviewPubMed Verified
- 29.Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis
Tajik N, Frech M, Schulz O, Schälter F, Lucas S, Azizov V et al. · Nature communications · 2020PubMed Verified
- 30.Therapeutic options for coeliac disease: What else beyond gluten-free diet?
Caio G, Ciccocioppo R, Zoli G, De Giorgio R, Volta U · Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver · 2020ReviewPubMed Verified
- 31.Differences in mechanisms underlying reinstatement of cigarette smoke extract- and nicotine-seeking behavior in rats
Cross SJ, Reynaga DD, Cano M, Belluzzi JD, Zaveri NT, Leslie FM · Neuropharmacology · 2020PubMed Verified
- 32.Intestinal Barrier Function in Gluten-Related Disorders
Cardoso-Silva D, Delbue D, Itzlinger A, Moerkens R, Withoff S, Branchi F et al. · Nutrients · 2019ReviewPubMed Verified
- 33.Agonist Selectivity and Ion Permeation in the α3β4 Ganglionic Nicotinic Receptor
Gharpure A, Teng J, Zhuang Y, Noviello CM, Walsh RM Jr, Cabuco R et al. · Neuron · 2019PubMed Verified
- 34.Virulence, antimicrobial and heavy metal tolerance, and genetic diversity of Vibrio cholerae recovered from commonly consumed freshwater fish
Xu M, Wu J, Chen L · Environmental science and pollution research international · 2019PubMed Verified
- 35.Evolving Therapy for Celiac Disease
Yoosuf S, Makharia GK · Frontiers in pediatrics · 2019ReviewPubMed Verified
- 36.Novel Nondietary Therapies for Celiac Disease
Alhassan E, Yadav A, Kelly CP, Mukherjee R · Cellular and molecular gastroenterology and hepatology · 2019ReviewPubMed Verified
- 37.Breaking Down Barriers: How Understanding Celiac Disease Pathogenesis Informed the Development of Novel Treatments
Valitutti F, Fasano A · Digestive diseases and sciences · 2019ReviewPubMed Verified
- 38.(Outcome) Measure for (Intervention) Measures: A Guide to Choosing the Appropriate Noninvasive Clinical Outcome Measure for Intervention Studies in Celiac Disease
Singh P, Silvester JA, Leffler D · Gastroenterology clinics of North America · 2019ReviewPubMed Verified
- 39.Nondietary Therapies for Celiac Disease
Serena G, Kelly CP, Fasano A · Gastroenterology clinics of North America · 2019ReviewPubMed Verified
- 40.Widespread distribution of prophage-encoded virulence factors in marine Vibrio communities
Castillo D, Kauffman K, Hussain F, Kalatzis P, Rørbo N, Polz MF et al. · Scientific reports · 2018PubMed Verified
- 41.Peptide therapeutics for the treatment of gastrointestinal disorders
Fretzen A · Bioorganic & medicinal chemistry · 2018ReviewPubMed Verified
- 42.The α3β4 nAChR partial agonist AT-1001 attenuates stress-induced reinstatement of nicotine seeking in a rat model of relapse and induces minimal withdrawal in dependent rats
Yuan M, Malagon AM, Yasuda D, Belluzzi JD, Leslie FM, Zaveri NT · Behavioural brain research · 2017PubMed Verified
- 43.Zonulin transgenic mice show altered gut permeability and increased morbidity/mortality in the DSS colitis model
Sturgeon C, Lan J, Fasano A · Annals of the New York Academy of Sciences · 2017PubMed Verified
- 44.The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate
Khaleghi S, Ju JM, Lamba A, Murray JA · Therapeutic advances in gastroenterology · 2016ReviewPubMed Verified
- 45.Pharmacological approaches in celiac disease
McCarville JL, Caminero A, Verdu EF · Current opinion in pharmacology · 2015ReviewPubMed Verified
- 46.High affinity α3β4 nicotinic acetylcholine receptor ligands AT-1001 and AT-1012 attenuate cocaine-induced conditioned place preference and behavioral sensitization in mice
Khroyan TV, Yasuda D, Toll L, Polgar WE, Zaveri NT · Biochemical pharmacology · 2015PubMed Verified
- 47.AT-1001 Is a Partial Agonist with High Affinity and Selectivity at Human and Rat α3β4 Nicotinic Cholinergic Receptors
Tuan EW, Horti AG, Olson TT, Gao Y, Stockmeier CA, Al-Muhtasib N et al. · Molecular pharmacology · 2015PubMed Verified
- 48.Pharmacotherapy: Quest for the quitting pill
Willyard C · Nature · 2015PubMed Verified
- 49.Non-dietary methods in the treatment of celiac disease
Szaflarska-Popławska A · Przeglad gastroenterologiczny · 2015ReviewPubMed Verified
- 50.Coformulation of a Novel Human α-Galactosidase A With the Pharmacological Chaperone AT1001 Leads to Improved Substrate Reduction in Fabry Mice
Xu S, Lun Y, Brignol N, Hamler R, Schilling A, Frascella M et al. · Molecular therapy : the journal of the American Society of Gene Therapy · 2015PubMed Verified
Medical disclaimer: This information is for educational purposes only and does not constitute medical advice. Many compounds listed are research chemicals not approved for human use. Always consult a qualified healthcare professional before starting any protocol.
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