Multi-Omics Insights into the Effects of Probiotics and Vitamin D on Clinical Signature, Inflammation, Metabolism, and Microbiota in Oral Lichen Planus: The MICROCOSM In Vivo Study

Oral lichen planus (OLP) is a chronic inflammatory oral disease associated with immune dysregulation and malignant transformation risk. Vitamin D and probiotics may modu-late immune and microbial pathways involved in OLP. In this study, we evaluated their effects on clinical outcomes and multi-omics profiles in 25 adult OLP patients. Vitamin D-deficient patients received 2,000 IU/day vitamin D3, and all participants received a probiotic blend (Limosilactobacillus reuteri LRE11, Lactica-seibacillus rhamnosus LR04, and Lacticaseibacillus casei LC04) for 16 weeks. Clinical assess-ments and analyses of saliva, serum, oral swabs, and stool samples were performed be-fore and after treatment. Following the intervention, 76% of participants achieved clinical remission. Significant metabolomic changes were observed mainly in saliva and feces. Serum cytokines, me-tabolites, and lipoproteins showed no significant differences. Microbiome profiling demonstrated treatment-related compositional shifts in oral and fecal samples, including increased Lacticaseibacillus abundance. Multi-omics integration identified coordinated in-teractions among microbial, metabolic, immune, and lipid pathways, highlighting inter-connected gut-oral biological responses. Combined vitamin D and probiotic supplementation was associated with clinical im-provement and coordinated oral-intestinal multi-omics changes, supporting a sys-tems-level understanding of OLP remission. These findings suggest that modulating the microbiota-metabolism-immunity axis could represent a promising therapeutic strategy for achieving sustained disease control and clinical remission.