Skip to content
Calculator
Evidence: LowPeptideResearch ChemicalPaneth cell α-defensinEndogenous antimicrobial peptideNot a drug

HD5

The small intestine's own antibiotic peptide, studied in Crohn's disease, coeliac disease and radiation injury

Human alpha-defensin 5, or HD5, is an antimicrobial peptide made by Paneth cells at the base of the small intestine's crypts. It helps decide which bacteria live against the gut lining. Researchers study it as a marker of intestinal immunity in Crohn's and coeliac disease, and as a possible treatment in animal models of gut injury. It is not a drug, and no human treatment trial has been published.

At a Glance Read Research →
Overview

What is it?

Paneth cells sit at the bottom of the small intestine's crypts and release granules full of antimicrobial proteins. HD5 is the most abundant of them. It is made as an inactive precursor and cut into its active form in the gut, where it kills or restrains bacteria and shapes the mix of microbes that live near the lining. Early work located it precisely: antibodies stained Paneth cells of the normal adult small intestine, and electron microscopy placed it in their secretory granules.

Because Paneth cell function falters in several diseases, HD5 is often measured as a marker. In coeliac disease, a probiotic strain lowered Paneth cell counts and HD5 expression, while a gluten-free diet did more to reduce macrophages. In Crohn's disease, tissue from patients let more of an adherent-invasive E. coli strain pass through the lining than tissue from controls, and pre-treating the tissue with HD5 reduced that passage.

Animal studies go further. In mice exposed to radiation, HD5 given in the diet before irradiation blocked much of the damage to the gut microbiota and barrier. None of this has been tested as a treatment in people, and HD5 is sold only as a research reagent.

Structured data

At a Glance

Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.

ClassA 32-amino-acid cationic antimicrobial α-defensin produced by small-intestinal Paneth cells — the dominant defensin of the human small bowel — and a key regulator of intestinal microbiota composition.
SequenceATCYCRTGRCATRESLSGVCEISGRLYRLCCR (disulfides Cys3-Cys31, Cys5-Cys20, Cys10-Cys30)
FormulaC144H238N50O45S6
Molecular weight3582.2 g/mol
Half-lifenot applicable — endogenous epithelial peptide
US statusResearch Chemical
Evidence levelLow
Last reviewed2026-09-30
Evidence

Published Research

These are studies of HD5, read from their PubMed abstracts.

Human2017

Coeliac disease: probiotic vs gluten-free diet

A gluten-free diet lowered duodenal macrophage counts more than Bifidobacterium infantis, while the probiotic lowered Paneth cell counts and expression of α-defensin-5 (P<0.001).

PMID: 27636409
In Vitro2021

Crohn's disease tissue and adherent-invasive E. coli

Follicle-associated epithelium from Crohn's patients allowed more bacterial translocation than control tissue, and incubation with HD5 reduced it in both.

PMID: 33336693
In Vitro1997

Where HD5 is made

Antibodies stained Paneth cells of the normal adult small intestine, electron microscopy placed HD5 in their secretory granules, and the precursor form was not cytotoxic to human intestinal cell lines.

PMID: 9169779
Animal2023

Radiation injury in mice

Radiation depleted intestinal α-defensins; dietary HD5 given 24 hours before irradiation significantly blocked radiation-induced changes in gut microbiota, permeability and endotoxaemia.

PMID: 37638013
Safety

Side Effects & Contraindications

Reported Side Effects

HD5 has not been given to people as a treatment.

● No human safety data for HD5 as a drug
● Laboratory studies found the precursor form non-toxic to intestinal cells
● Effects in people are unknown

Contraindications & Cautions

There is no approved use.

● Not a medicine or supplement
● Research reagent only
● No dose exists
Questions

Frequently Asked Questions

?What is HD5?

Human alpha-defensin 5, an antimicrobial peptide made by Paneth cells in the small intestine that helps control the bacteria living next to the gut lining.

?Is HD5 a treatment?

No. It is studied as a marker of gut immunity and tested as a treatment only in animals and tissue samples.

?Why is it studied in Crohn's disease?

Paneth cell function is impaired in some people with Crohn's disease, and HD5 reduced the passage of an invasive E. coli strain through patients' intestinal tissue in the laboratory.

Bibliography

References

  1. [pubmed] Pinto-Sánchez MI, et al. "Bifidobacterium infantis NLS Super Strain Reduces the Expression of α-Defensin-5, a Marker of Innate Immunity, in the Mucosa of Active Celiac Disease Patients." J Clin Gastroenterol, 2017;51(9):814-817. PMID: 27636409.
  2. [pubmed] Alkaissi LY, et al. "Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn's Disease." Inflamm Bowel Dis, 2021;27(7):1116-1127. PMID: 33336693.
  3. [pubmed] Porter EM, et al. "Localization of human intestinal defensin 5 in Paneth cell granules." Infect Immun, 1997;65(6):2389-95. PMID: 9169779.
  4. [pubmed] Shukla PK, et al. "Paneth cell dysfunction in radiation injury and radio-mitigation by human α-defensin 5." Front Immunol, 2023;14:1174140. PMID: 37638013.

Sources & Citations

Every study on this page was read from its PubMed record; for approved products, indications and pharmacology come from the FDA label on DailyMed and approval details from Drugs@FDA, read September 30, 2026. Grey Peptides sells nothing and links to no vendor.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.

Last reviewed: 2026-09-30