Impact of OMICS Technologies in Our Understanding of the Pathogenesis of Peri‐Implantitis

ABSTRACT Objectives To evaluate the contribution of OMICS technologies to the understanding of peri‐implantitis pathogenesis from a host immune perspective. Materials and Methods A narrative review was conducted based on electronic searches of PubMed, MEDLINE, and Google Scholar up to October 2025, complemented by manual screening of reference lists. Search terms combined “peri‐implantitis” with OMICS‐related keywords, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, RNA sequencing, single‐cell and spatial transcriptomics, multi‐omics, and machine learning. Studies were selected based on clinical relevance and their contribution to understanding peri‐implantitis pathogenesis from a host immune perspective. Results Among the studies included, most focused on transcriptomic analyses, while fewer investigated genomics, epigenomics, proteomics, or metabolomics. Integration across OMICS layers highlights peri‐implantitis as a multilayered host–microbiome molecular ecosystem. Genomic variants affecting metal ion binding, cytoskeletal organization, and cell adhesion may predispose tissues to heightened immune sensitivity. Epigenomic analyses revealed differential DNA methylation of immune‐regulatory and signaling genes, linking environmental exposures, such as smoking, to altered host responses. Transcriptomic studies, including bulk, single‐cell, and spatial approaches, demonstrated dysregulated immune signaling, pro‐inflammatory fibroblast–neutrophil interactions, oxidative stress, and dysregulated tissue remodeling. Proteomic profiling of peri‐implant crevicular fluid confirmed elevated neutrophil‐derived antimicrobial proteins and inflammatory mediators, reflecting active host defense responses. Metabolomic studies identified disease‐specific alterations in amino acids, organic acids, and polyamines, which correlate with pathogenic microbial taxa and modulate immune and tissue responses. Collectively, these findings reveal convergent pathways of immune dysregulation, extracellular matrix disruption, tissue remodeling, and host–microbiome crosstalk as central features of peri‐implantitis. Conclusions OMICS analyses show that peri‐implantitis is a complex host–microbiome molecular ecosystem. Integrated molecular insights provide a foundation for biomarker development, predictive diagnostics, and targeted interventions. However, future studies with larger cohorts and functional validation are needed to support clinical translation.