Microbiota and antibiotic exposure in sarcoidosis.

Background: Sarcoidosis is a multisystem granulomatous disorder characterized by excessive immune activation in genetically predisposed individuals. Despite decades of investigation, its etiology remains unresolved. Emerging evidence indicates that disruptions in host-microbiota homeostasis may contribute to immune dysregulation and disease persistence, challenging the traditional view of sarcoidosis as a purely immune-mediated condition. Perspective: Recent findings have revealed alterations in both respiratory and intestinal microbiota among patients with sarcoidosis, suggesting that microbial dysbiosis may influence T-cell polarization and granulomatous inflammation. Antibiotic exposure, particularly to macrolides and tetracyclines, represents a largely overlooked modifier that may alter this equilibrium through combined microbiota-dependent and immunomodulatory mechanisms. Given the frequent use of antibiotics in these patients for respiratory infections or off-label anti-inflammatory purposes, understanding their effect on microbial diversity, immune signaling, and disease course warrants systematic evaluation. Translational Outlook: We propose an integrative framework combining microbiota profiling, immune phenotyping, and therapeutic exposure to delineate microbiota-immunity interactions in sarcoidosis. Multi-omics strategies, supported by advanced computational and network-based analyses, could uncover microbe-immune signatures predictive of chronicity or treatment response. Defining how antibiotics shape these interactions may provide a foundation for microbiota-informed, immune-targeted, and ultimately personalized interventions. Conclusion: Deciphering the interplay between microbiota composition, antibiotic exposure, and immune regulation has the potential to reshape our understanding of sarcoidosis pathogenesis and to guide the development of precision-based therapeutic strategies.