Metabolomics Applications for Diagnosing Peri-Implantitis: A Systematic Review of In Vivo Studies

Background/Objectives: Peri-implantitis is a prevalent inflammatory condition affecting dental implants, leading to increased treatment costs, patient dissatisfaction, and potential implant failure. Novel biomarker-based approaches may contribute to early detection, thereby decreasing the burden of the disease. The aim of this review was to assess in vivo studies using metabolomics to identify the metabolic profiles and potential biomarkers of peri-implantitis. Methods: The protocol for this study was registered with PROSPERO (CRD42025634865). Five databases and grey literature sources (PubMed, Scopus, Web of Science, ProQuest, and Google Scholar) were searched using keywords related to metabolomics and peri-implantitis. Studies were selected by independent, inter-calibrated researchers. Data were extracted using predefined, custom forms. The risk of bias was assessed using the ROBINS-I tool. Results: An electronic literature search retrieved 543 articles, of which five were selected. All studies were published within the last five years of the search. All but one study used untargeted metabolomics, and all studies identified metabolites associated with peri-implantitis or distinct metabolomic profiles of peri-implantitis. SCFAs and lysine metabolites were recurring in the results, confirming the findings of previous metabolomic studies on periodontal disease. Conclusions: Metabolomics has not been widely used to study peri-implantitis. Evidence from existing studies confirms the findings of metabolomics studies on periodontitis. Several metabolites related to PI are associated with immune response, tissue degradation, and cellular energy pathways. Integrating -omics technologies into peri-implantitis diagnosis may facilitate biomarker discovery and improve early detection strategies.