Periodontitis and Systemic Disease: How Much More Evidence do we Need?

Periodontitis is not just a condition of the mouth. It is a chronic inflammatory disease with potential effects on numerous organ systems of the body. The periodontopathic bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can enter the systemic circulation from the periodontal pocket and have an impact on the body's organs distant from the oral cavity. To review the links between periodontitis and nine systemic disease domains, distinguishing mechanistic, observational, interventional, and causal evidence. This narrative review was supported by a systematic search of PubMed/MEDLINE, the Cochrane Library, and Scopus between January and June 2026. The majority of the reviews used in this paper are peer-reviewed journal articles published between 2016 and 2026. These articles include review articles, evidence-based studies such as Mendelian randomization studies, umbrella reviews, and reviews from professional organizations such as the European Federation of Periodontology, the World Heart Federation, and WONCA Europe. The evidence is strongest for diabetes mellitus, where the relationship (as explained later on) is bidirectional and periodontal treatment reduces HbA1c by 0.43% at 3–4 months. For cardiovascular disease, associations are consistent, but treatment trials with cardiovascular events are lacking. Mendelian randomization findings are mixed, and the links with pregnancy outcomes and neurological conditions remain conflicting or mainly mechanistic. Additionally, a relatively new concept in the fields of immunology and inflammation is discussed, namely the phenomenon of trained immunity and myelopoiesis as a potential explanation for the systemic inflammatory effects of periodontitis even after the periodontal infection has resolved. The evidence presented in this paper indicates that periodontitis is a disease with multiorgan system involvement that merit a place within the medical disciplines beyond dentistry alone, most clearly in endocrine (especially for diabetes patients) and cardiovascular care, while trials with clinical endpoints are still needed for most other domains.