Lipopeptides from commensal bacteria may inhibit AD flares

Staphylococcus aureus. Photo by Janice Haney Carr, provided by CDC/ Matthew J. Arduino, DRPH, via Wikimedia Commons

New findings suggest that commensal bacteria on the skin release molecules that inhibit the skin’s production of pro-inflammatory interleukin (IL)-33, potentially preventing atopic dermatitis (AD) flares.

Published in Nature Communications, the findings come from research conducted at the University of Manchester and Tokyo University of Agriculture and Technology.

The research team had previously demonstrated that Staphylococcus aureus-derived Second immunoglobulin-binding protein (Sbi) drives type 2 immune responses and AD.

In this new research, they found that when nutrients run low, many friendly staphylococcal species release lipopeptides as they age, which calm the skin’s immune response.

When investigators applied the lipopeptides to the skin of mice, it prevented the release of IL‑33 and stopped AD from developing.

 “We have previously already shown that blocking IL‑33 with a biologic drug stops eczema in the same mouse model,” said study author Professor Akane Tanaka, PhD, from Tokyo University of Agriculture and Technology, in a press release. “Now we’ve shown that bacteria can do it themselves- an exciting and potentially game-changing discovery.”

Diacylated lipopeptides were the most effective, while monoacylated versions had no effect. The molecules blocked IL‑33 from leaving the nucleus, trapping it in the perinuclear space, preventing it from driving inflammation.

Study author Professor Hiroshi Matsuda, PhD, from Tokyo University of Agriculture and Technology, said: “Our findings overturn long‑held assumptions about how bacterial molecules behave. Instead of triggering immune alarms through TLR pathways, these lipopeptides bypass them entirely. The next step is testing these lipopeptides in people with eczema to see if they can be turned into real‑world treatments.”

This discovery, the authors say, could lead to a new class of safe, stable treatments that could help millions living with skin and other allergic diseases. The authors write that their findings confirm their suspicion that beneficial bacteria may naturally counteract the AD-driving effects of Staphylococcus aureus.

Peter Arkwright, PhD, from The University of Manchester, said: “We think this is a very exciting result as lipopeptides are small, stable, non-infectious chemical structures that have the potential to be used as a topical treatment for eczema. They might also be used in the future to treat other allergic diseases such as hay fever.”

The study was supported by the LEO Foundation and the Japan Society for the Promotion of Science.