PERIOMED ORIGINAL 02 · EDITORIAL PERSPECTIVE30 SEPTEMBER 2026

AN EMERGING QUESTION

Can periodontal inflammation leave an immune memory?

Why trained immunity is becoming part of the conversation about oral inflammation and cardiovascular biology.

FIRST AUTHORHamail FazilMedical Sciences Scientific Coordinator & Expert Engagement · Pakistan

SECOND AUTHORThami Ouazzani-Touhami, MDMedical Sciences · Morocco

SCIENTIFIC REVIEWERLorenzo Maria Laudiero, DDSOral & Periodontal Sciences · Italy

THE IDEA IN BRIEF

Inflammation is often described as a response that begins, resolves and disappears. Research into trained immunity asks whether some inflammatory exposures can leave innate immune cells more responsive to later challenges.

In periodontitis, this raises an important possibility: repeated microbial and inflammatory signals from diseased periodontal tissues may influence immune activity beyond the mouth. Whether this contributes meaningfully to cardiovascular disease in humans is not yet established — but it is a question worth investigating.

ONE CONCEPT · FOUR MOMENTS

From repeated exposure to a potentially altered response.

01Periodontal inflammationA dysbiotic and persistently inflamed environment

→

02Systemic exposureMicrobial products and inflammatory mediators

→

03Innate immune adaptationPossible functional and epigenetic changes

→

04Later responsesPotentially amplified inflammatory signaling

This is a proposed biological framework. It does not demonstrate that periodontitis causes cardiovascular disease.

The immune system does not always return to exactly where it started.

Periodontitis is a chronic inflammatory disease shaped by a dysbiotic periodontal microbiota and a dysregulated host response. Although its clinical manifestations occur around the teeth, the inflammatory environment is not necessarily confined to the periodontal pocket. Consensus reports, cardiovascular statements and meta-analytic evidence recognize a consistent association between periodontitis and atherosclerotic cardiovascular disease, while emphasizing that association does not by itself demonstrate causality. [1] [2] [3]

Inflamed periodontal tissues form a highly vascular interface between microbial communities and the host. Ulceration of the pocket epithelium may allow microbial products and locally generated inflammatory mediators to reach the circulation. This provides several biologically plausible routes through which periodontal inflammation could interact with systemic inflammatory processes. [4]

Trained immunity adds another dimension to this discussion. It describes a form of innate immune adaptation in which an initial microbial or inflammatory stimulus is followed by metabolic and epigenetic changes that influence the response to a later challenge. [5]

This differs from classical adaptive immune memory. It is not based on a highly specific response to one antigen, and it may be helpful or harmful depending on context. Enhanced responsiveness can support host defence, but persistent or maladaptive training may contribute to chronic inflammatory states.

A plausible link, with important limits.

Several pathways may converge

Periodontitis is associated with systemic inflammatory markers, endothelial dysfunction and cardiovascular disease. Proposed pathways include intermittent microbial dissemination, the systemic effects of cytokines, oxidative stress, leukocyte activation and changes in endothelial signaling. These routes should be understood as complementary rather than as one simple movement of disease from the mouth to the heart. [1] [4] [6]

Inflammatory mediators can promote endothelial activation and adhesion-molecule expression, while oxidative stress may reduce nitric oxide bioavailability and impair vasodilation. Periodontal treatment has been associated with improvements in selected inflammatory and endothelial surrogate markers, including flow-mediated dilation; however, the evidence is heterogeneous, concerns surrogate outcomes and does not demonstrate prevention of cardiovascular events. [2] [6] [7]

A signal from trained-immunity research

Transient in vitro exposure to Porphyromonas gingivalis has produced increased IL-6 and TNF-α responses after later restimulation of human monocytes. This training-like response supports the biological possibility that periodontal microbial exposure may influence subsequent innate immune behavior. [8]

The human component of the same exploratory study produced a more cautious picture. Patients showed signs of systemic inflammation and haematopoietic tissue activation, but their circulating monocytes did not demonstrate a hyper-responsive phenotype and vascular inflammation was not increased. Experimental and human observations therefore need to be interpreted separately.

From circulating cells to the bone marrow

Innate immune memory may not be limited to short-lived mature monocytes. Experimental research in other inflammatory settings suggests that cytokines and microbial signals can influence haematopoietic stem and progenitor cells, generating a longer-lasting bias toward inflammatory myeloid responses. This concept is sometimes described as central trained immunity. [5]

Animal models of periodontitis provide support for persistent inflammatory changes in bone-marrow progenitors. Direct evidence of comparable, durable reprogramming in human periodontitis remains limited, and its clinical cardiovascular relevance is not yet known.

03 · HOW THE HYPOTHESIS DEVELOPS

Not one leap, but a sequence of testable steps.

Local inflammatory exposure

Dysbiosis and ulcerated periodontal tissues create repeated contact between microbial products, inflammatory mediators and the host circulation.

Innate immune activation

Pattern-recognition pathways in monocytes, macrophages and neutrophils respond to microbial and inflammatory signals.

Functional reprogramming

Metabolic and epigenetic changes may alter how these cells — or their progenitors — respond to later stimulation.

Vascular relevance

A heightened inflammatory response could interact with endothelial activation and other processes involved in atherosclerotic biology.

Each stage has a different level of evidence. Connecting them into a complete causal pathway in humans remains the central scientific challenge.

04 · WHAT REMAINS UNKNOWN

The missing evidence matters.

Whether immune training caused by periodontal exposure persists after successful treatment.
Whether changes observed in experimental models also occur in human bone-marrow progenitors.
Whether one organism is particularly important or the wider dysbiotic community drives the response.
How trained immunity could be measured reliably in an individual patient.

05 · WHAT COULD COME NEXT

Questions that can be tested.

Longitudinal immune profiling before and after periodontal therapy.
Functional restimulation studies combined with epigenetic and metabolic analyses.
Research connecting periodontal status, immune phenotypes and vascular outcomes over time.
Better-powered studies that distinguish surrogate markers from clinical cardiovascular events.

THE QUESTION TO CARRY FORWARD

Could recurrent inflammation in one biological environment change how the body responds in another?

Trained immunity gives oral-systemic research a new way to formulate this question. Its value currently lies not in proving a completed causal pathway, but in connecting periodontal biology, innate immunity and cardiovascular research within a testable scientific framework. It also reinforces a broader principle: oral inflammation should be studied within the biology of the whole person, while the limits of the available evidence remain clearly visible.

SELECTED SOURCES

Continue exploring the evidence.

This page is an independent public-facing editorial perspective. It is not a preprint, does not reproduce a manuscript submitted for publication and should not be cited as the author’s scientific review.