Study Links Skin Microbiota and AD Alleviation via Melatonin

Key Takeaways

• Melatonin alters the skin microbiota in AD mice, increasing microbiota-derived SCFAs, particularly propionic acid.
• Propionic acid suppresses FABP5 expression through GPR43, reducing AD symptoms in both mice and HaCaT cells.
• Targeting the skin microbiota using melatonin or SCFA-related pathways offers a new potential treatment pathway. 

A new study published in the Journal of Allergy and Clinical Immunology indicates melatonin has been shown to reduce atopic dermatitis (AD) symptoms by altering skin microbiota composition, with short-chain fatty acids (SCFAs) such as propionic acid playing a key role in this process.

Although the results came from a mouse model of AD, the study researchers showed that melatonin treatment reshaped the skin’s bacterial composition. Skin microbiota transplantation experiments confirmed that these changes were integral to alleviating AD symptoms. Melatonin-treated mice exhibited increased levels of propionic acid, a microbiota-derived SCFA. Propionic acid suppressed the expression of fatty acid-binding protein 5 (FABP5), which is implicated in AD pathology.

Further investigations in HaCaT cells showed propionic acid's effects on FABP5 expression were mediated through the activation of the G-protein-coupled receptor 43 (GPR43). Blocking GPR43 using the inhibitor GLPG0974 reversed the therapeutic effects of melatonin in vitro and in vivo. 

"Our study demonstrates that melatonin alleviates AD through skin microbiota/propionic acid/GPR43/FABP5 axis, highlighting a novel role of melatonin as a modulator of skin microbiota to alleviate AD," the authors wrote.

Yang L, et al. Journal of Allergy and Clinical Immunology. 2024. Doi:10.1016/j.jaci.2024.11.019