Exploring the interplay between GLP-1 and short-chain fatty acids in modulating immune responses in skin

• Grant number: 25/01194-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Hosana Gomes Rodrigues
• Grantee: Roberta Nicolli Sagiorato
• Supervisor: Raymond Cho
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: University of California, San Francisco (UCSF), United States
• Associated to the scholarship: 22/05395-2 - Effects of oral butyrate treatment on crosstalk between memory resident T cells and dendritic cells during experimental psoriasis., BP.DR

Abstract

Glucagon-like peptide-1 (GLP-1) is a hormone produced by intestinal endocrine cells that regulates glucose metabolism by stimulating insulin secretion and inhibiting glucagon release. GLP-1 receptors (GLP-1Rs) are expressed in several organs, including the skin, where they can affect keratinocytes, the primary cells involved in the development of psoriasis. In psoriasis, T-cell activation contribute to abnormal skin cell proliferation, leading to the formation of red, scaly lesions. Furthermore, psoriasis is associated with systemic conditions such as obesity and diabetes, making controlling inflammation crucial for disease management. Butyrate, a short-chain fatty acid produced by the gut microbiota, has shown promise as a therapeutic for psoriasis due to its anti-inflammatory effects. In murine models, butyrate has been shown to reduce skin thickness in psoriasis model through the GPR43 receptor. In parallel, activation of the GLP-1R not only improves glucose, but may also influence the composition of the gut microbiota by promoting butyrate production. In this sense, we hypothesized that administration of GLP-1 to non-psoriatic patients will modify the gut microbiota, leading to an increase in the prevalence of butyrate-producing bacteria. This study aims to explore the relationship between butyrate, GLP-1 and healthy skin in non-psoriatic individuals using GLP-1 analogues. Specifically, we will assess serum concentrations of SCFAs, conduct metagenomic analyses on fecal samples, and perform single-cell RNA sequencing on skin samples. These efforts will help us better understand the mechanisms that link GLP-1 and SCFAs in maintaining healthy skin. Ultimately, we plan to analyze and integrate these data to establish how GLP-1 and SCFAs may contribute to improving psoriasis symptoms. (AU)