Microbiota-fibroblast crosstalk represents the missing link in skin barrier dysfunction and fibrosis.

Abstract

Dermal fibroblasts are key cellular components of the skin stroma, primarily responsible for extracellular matrix synthesis and the maintenance of tissue structure and function. Beyond this canonical role, these cells also possess immune regulatory functions, enabling them to sense and integrate microbial cues to orchestrate cutaneous inflammatory responses, wound repair and fibrogenesis. The skin microbiome is a critical regulator of fibroblast homeostasis; its dysbiosis disrupts fibroblast-microbe crosstalk, leading to aberrant fibroblast activation and contributing to the pathogenesis of various dermatological conditions. Clinically, the burden of these disorders is substantial, and current therapeutic strategies targeting fibroblast dysfunction often yield limited efficacy. Fortunately, recent advances in deciphering the pathophysiological mechanisms underlying fibroblast-microbe interactions have highlighted critical molecular regulatory networks, opening new therapeutic avenues. Among these emerging approaches, interventions targeting the microbiota-fibroblast axis - such as probiotics, postbiotics and fibroblast-directed agents - hold considerable promise. Deciphering the nuances of this crosstalk is pivotal for advancing precision and regenerative therapies, with potential implications for cutaneous and systemic fibrotic disorders.