The impact of commensal microbiota on dermal matrisome

Summary: Abstract Body: As the body's outermost barrier, the skin provides crucial protection against external insults. This protective function is underpinned by the dermis, which constitutes most of the skin's volume and serves as its architectural framework. While the role of commensal microbiota in maintaining skin barrier has begun to gain attention, how the microbiota influences the dermis and dermal fibroblasts remains largely unknown. Here, we demonstrate that microbiota induce distinct patterns of matrisome expression, particularly in the collagen biosynthesis pathway, within the dermis of germ-free (GF) and conventionally-raised (CR) mice. Histological and hydroxyproline analyses revealed lower collagen content and less intricate collagen organization in the dermis of GF mice. A healthy matrisome is crucial as it provides a biophysical scaffold for cell anchorage and migration, while also regulating biochemical signals for cell activation. Indeed, primary fibroblasts derived from GF mice exhibited reduced activation capacity in both transwell migration and in vitro wound healing assays. Notably, replacement with CR matrisome restored the activation capacity of GF fibroblasts. These findings suggest that the microbiota contribute to the structural and functional integrity of the skin by modulating dermal matrisome expression. Jamie Pan¹, Aayushi Uberoi², Elizabeth Grice¹ 1. Department of Dermatology, University of Pennsylvania, Philadelphia, PA, United States. 2. Department of Pathology & Immunology, Washington University in St Louis, St. Louis, MO, United States. Innate Immunity, Microbiology, and Microbiome