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Larazotide Acetate

Limited human data

Also known as: AT-1001 · zonulin-antagonist peptide

A first-in-class oral peptide designed to keep intestinal tight junctions closed, studied as an adjunct therapy for celiac disease alongside a gluten-free diet. One of the more rigorously trialed gut-health peptides, with multiple completed phase 2 RCTs.

Mechanism (plain language)

Acts locally in the gut lumen (not absorbed systemically at meaningful levels) to inhibit tight-junction opening, aiming to reduce paracellular passage of gluten peptides into the intestinal lining that triggers immune activation in celiac disease.

What research suggests

Multiple randomized, placebo-controlled trials during gluten challenge report reduced gluten-induced gastrointestinal symptoms and lower antibody responses at some doses, though the primary permeability biomarker (lactulose/mannitol ratio) has not consistently differed from placebo across trials.

Uncertainties & risks

Results are mixed across the four completed RCTs, with a systematic review noting symptom benefit during gluten challenge but no consistent effect on the core permeability endpoint. Not FDA-approved; not a substitute for a gluten-free diet in celiac disease, and there's no meaningful evidence for use in healthy people without celiac disease.

Primary sources

Secondary citations for verification. Prefer the STACKD summary above for context before opening these.