Purpose To evaluate and synthesize the existing evidence on the microbiological and human immune response associated with peri‐implantitis in comparison to healthy implants. Materials and methods Three electronic databases (MEDLINE, Embase, and Cochrane Library) were searched in October 2019 to identify clinical studies evaluating the microbiota and the immune response associated with peri‐implantitis. Two reviewers independently screened the studies and used the full text to extract the data. A qualitative synthesis was performed on the extracted data and summary tables were prepared. Due to clinical and methodological heterogeneity among included studies, no meta‐analysis was performed. Results Forty studies were included in this review. Of these, 20 studies compared the microbiological profile of peri‐implantitis with healthy implants. Nineteen studies focused on the immune response associated with peri‐implantitis in comparison to healthy implants. Three studies focus on gene polymorphism associated with peri‐implantitis. The most commonly reported bacteria associated with peri‐implantitis were obligate anaerobe Gram‐negative bacteria (OAGNB), asaccharolytic anaerobic Gram‐positive rods (AAGPRs), and other Gram‐positive species. In regard to immune response, the most frequently reported pro‐inflammatory mediators associated with peri‐implantitis were IL‐1β, IL‐6, IL‐17, TNF‐α. Osteolytic mediator, e.g., RANK, RANKL, Wnt5a and proteinase enzymes, MMP‐2, MMP‐9, and Cathepsin‐K were also expressed at higher level in peri‐implantitis sites compared to control. Conclusions Peri‐implantitis is associated with complex and different microbiota than healthy implants including bacteria, archaea, fungi, and virus. This difference in the microbiota could provoke higher inflammatory response and osteolytic activity. All of this could contribute to the physiopathology of peri‐implantitis.

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