HD6
The gut's own defensin that does not kill bacteria but entangles them, and is lower in the small intestine of people with Crohn's disease
Human α-defensin 6 (HD6) is a 32-residue peptide made by Paneth cells at the base of small-intestinal crypts. Unlike other defensins it barely kills bacteria in a dish; a 2012 Science paper showed it instead self-assembles into fibres that surround and trap them. It is a research subject, not a treatment.
What is it?
Paneth cells guard the stem cells of the small intestine by releasing antimicrobial proteins into the crypt. HD6 was identified there in 1993 as an abundant defensin message, but for years it was a puzzle, because in standard tests it killed almost nothing.
The answer came in 2012: HD6 binds bacterial surface proteins and then assembles, molecule on molecule, into fibrils and nets that wrap the bacteria and stop them invading the gut lining. Later work found the same trapping blocks Candida from sticking to and invading intestinal cells, and that HD6 can bind and neutralise toxins of Clostridioides difficile. Laboratory analogues traced its weak killing to an unusual arrangement of arginines.
In people, lower HD6 in the small intestine has been linked to Crohn's disease. Nobody has given HD6 as a treatment, and peptides sold online under this name have no human data behind them.
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.
Published Research
Studies whose titles name HD6, read from their PubMed abstracts on October 4, 2026; the Crohn's disease paper is the human one.
Nanonets
HD6 protected against invasion by enteric bacteria in cells and in mice. After binding bacterial surface proteins it self-assembled into fibrils and nanonets that entangled the bacteria, in vivo as well as in vitro, and the assembly needed histidine-27.
Lower in Crohn's disease
In noninflamed jejunum sampled by balloon endoscopy from 15 patients with Crohn's disease and 9 controls, HD6, but not HD5, was reduced; in HD6-negative crypts, nuclear beta-catenin was impaired. In cells, Atoh1 and beta-catenin together drove the HD6 promoter.
Blocking Candida
HD6 blocked Candida albicans from adhering to human intestinal cells and suppressed its invasion and biofilm formation; a variant that cannot assemble lost the effect, so self-assembly is required.
Neutralising C. difficile toxins
HD6 bound the toxins TcdA and TcdB directly, rapidly forming complexes, and protected human cells, model gut barriers and zebrafish embryos from their effects.
Why it kills so little
A linear HD6 analogue with arginines redistributed like active defensins became broadly antimicrobial, pointing to HD6's unusual arginine pattern as the reason it does not kill bacteria directly.
Side Effects & Contraindications
Reported Side Effects
No human safety data exist, because HD6 has never been given to people.
Contraindications & Cautions
None established.
Legal Status
An endogenous human peptide studied in the laboratory; not a drug anywhere.
Frequently Asked Questions
?What is HD6?
Human α-defensin 6, an antimicrobial peptide made by Paneth cells in the small intestine.
?How does HD6 fight bacteria if it does not kill them?
It self-assembles into fibrils and nanonets that trap bacteria and stop them invading the gut lining, as a 2012 Science paper showed.
?Is HD6 linked to Crohn's disease?
Lower HD6 has been found in the small intestine of people with Crohn's disease, including noninflamed tissue.
?Can you take HD6?
It has never been given to people in a study; it is a research subject, not a treatment.
References
- [pubmed] Chu H, et al. "Human α-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets." Science, 2012;337(6093):477-81. PMID: 22722251.
- [pubmed] Hayashi R, et al. "Reduced Human α-defensin 6 in Noninflamed Jejunal Tissue of Patients with Crohn's Disease." Inflamm Bowel Dis, 2016;22(5):1119-28. PMID: 26891258.
- [pubmed] Chairatana P, et al. "Human α-Defensin 6 Self-Assembly Prevents Adhesion and Suppresses Virulence Traits of Candida albicans." Biochemistry, 2017;56(8):1033-1041. PMID: 28026958.
- [pubmed] Barthold L, et al. "Human α-Defensin-6 Neutralizes Clostridioides difficile Toxins TcdA and TcdB by Direct Binding." Int J Mol Sci, 2022;23(9). PMID: 35562899.
- [pubmed] Mathew B, et al. "Antimicrobial activity of human α-defensin 6 analogs: insights into the physico-chemical reasons behind weak bactericidal activity of HD6 in vitro." J Pept Sci, 2015;21(11):811-8. PMID: 26400692.
- [pubmed] Jones DE, et al. "Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel." FEBS Lett, 1993;315(2):187-92. PMID: 8417977.
- [pubmed] Wehkamp J, et al. "Reduced Paneth cell alpha-defensins in ileal Crohn's disease." Proc Natl Acad Sci U S A, 2005;102(50):18129-34. PMID: 16330776.
Sources & Citations
Studies from their PubMed abstracts, October 4, 2026. The 1993 discovery paper and the 2005 Crohn's disease paper are listed as references because their titles name the defensin family rather than HD6.
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.