TY - JOUR
T1 - Microbiota modulation by a human Paneth cell α-defensin fragment protects against DSS-induced colitis
AU - Bonazzi, Erica
AU - Hao, Fuhua
AU - Patterson, Andrew D.
AU - Peyrin-Biroulet, Laurent
AU - Jensen, Benjamin A.H.
AU - Chassaing, Benoit
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2026/1/16
Y1 - 2026/1/16
N2 - The gastrointestinal tract hosts a diverse microbial community, named the intestinal microbiota, which plays a vital role in gut health. Host defense peptides (HDPs), such as defensins, help regulate interactions between the host and its microbiota. Dysfunction in HDPs expression has been associated with a greater risk of inflammatory bowel diseases (IBDs), while some HDPs may positively shape the gut environment. Human alpha defensin 5 (HD5) can be cleaved by intestinal enzymes into bioactive fragments such as HD51-9. In this study, we screened various HDPs (LL-37, hBD2, HD5, and HD51-9) for their modulatory effects on healthy human microbiotas in vitro and found distinct, donor-specific effects, with HD51-9 showing the strongest functional impact. Testing HD51-9 in a mouse colitis model revealed potent and microbiota-dependent protection against DSS-induced inflammation, partly through the beneficial of mucus-microbiota interactions.
AB - The gastrointestinal tract hosts a diverse microbial community, named the intestinal microbiota, which plays a vital role in gut health. Host defense peptides (HDPs), such as defensins, help regulate interactions between the host and its microbiota. Dysfunction in HDPs expression has been associated with a greater risk of inflammatory bowel diseases (IBDs), while some HDPs may positively shape the gut environment. Human alpha defensin 5 (HD5) can be cleaved by intestinal enzymes into bioactive fragments such as HD51-9. In this study, we screened various HDPs (LL-37, hBD2, HD5, and HD51-9) for their modulatory effects on healthy human microbiotas in vitro and found distinct, donor-specific effects, with HD51-9 showing the strongest functional impact. Testing HD51-9 in a mouse colitis model revealed potent and microbiota-dependent protection against DSS-induced inflammation, partly through the beneficial of mucus-microbiota interactions.
UR - https://www.scopus.com/pages/publications/105024736649
UR - https://www.scopus.com/pages/publications/105024736649#tab=citedBy
U2 - 10.1016/j.isci.2025.114310
DO - 10.1016/j.isci.2025.114310
M3 - Article
AN - SCOPUS:105024736649
SN - 2589-0042
VL - 29
JO - iScience
JF - iScience
IS - 1
M1 - 114310
ER -
