Why aren't you getting better – even if you eat healthily and take medication?

What is really happening to you?

Bleeding gums are not a matter of "normal sensitivity," but rather a sign of inflammation. Microbes and inflammatory mediators (e.g., IL-6, TNF-α, CRP) can enter the bloodstream with every meal or brushing, keeping the immune system in a low but persistent "state of disturbance." This condition is associated with metabolic and cardiovascular risks.

When oral bacteria migrate

The key pathogen of periodontitis, Porphyromonas gingivalis, has been found in various body tissues, and its spread and impact have been associated with several systemic conditions. A 2019 study identified traces of P. gingivalis in the brain tissue of Alzheimer’s disease patients and described the potential of gingipain inhibitors; this forms a correlation, not a proven causality.
Animal and mechanistic studies have shown that P. gingivalis from the mouth can alter gut microbiota and promote systemic inflammation.
The role of oral bacteria in atherosclerosis and complications of pregnancy (including placental findings) has also been described – evidence shows a consistent association, while causality remains a topic of debate across disciplines.

What do the numbers and reviews say?

• Diabetes and periodontitis. The relationship is bidirectional: diabetes increases the risk of periodontitis by approximately three times, and treating periodontitis can temporarily improve glycemic control. A 2022 Cochrane update found moderate certainty evidence that subgingival instrumentation reduces HbA1c by ~0.4% (on average). In short-term previous summaries, the effect was ~0.29% after 3–4 months.

• Cardiovascular diseases. High-quality systematic reviews indicate that periodontitis is associated with a ~1.24–1.34 times higher risk of coronary disease; the relationship for stroke has also been shown in multiple meta-analyses. Causality is not considered definitively proven, but biological plausibility and a consistent pattern of findings support the significance of the association.

How to interpret CRP?

In the context of cardiovascular risk and with high-sensitivity methods (hs-CRP), the following is considered:

• <1 mg/L – low risk

• 1–3 mg/L – moderate risk

• 
  

3 mg/L – high risk
These thresholds come from the joint recommendations of the CDC/AHA.

Rapid test for mapping inflammation: aMMP-8

aMMP-8 (active matrix metalloproteinase-8) oral rinse or periodontal pocket rapid test helps identify active tissue damage in periodontitis and monitor treatment effects. Many studies have used a cutoff value of ~20 ng/mL, which distinguishes health from disease; optimal cutoff points may vary slightly by device and sample type.

What does this mean for the patient?

• The oral cavity is not a "separate system" – it is part of immunity, metabolism, and cardiovascular regulation.

• If you have persistent fatigue, bleeding gums, bad breath, unstable blood sugar, or elevated hs-CRP, it is worth ruling out chronic inflammation of the oral cavity.

• Treating periodontitis may improve systemic markers (e.g., HbA1c) and vascular indicators; the effect is most clearly seen in the short term and requires maintenance care to persist.

Five practical steps

1. Look in the mirror. Bleeding, redness, swelling, or tooth mobility are warning signs – book an appointment.

2. Check hs-CRP. If the value is >3 mg/L, discuss with your family doctor whether there could be a source of inflammation in the mouth.

3. Ask for an aMMP-8 test. It helps differentiate active tissue breakdown and guide treatment.

4. Don’t wait for pain. Periodontitis often progresses without pain and can significantly damage bones before symptoms appear.

5. Maintenance care. Brushing with an electric toothbrush 2× a day, daily flossing/interdental brushes, and professional care 2× a year; quitting smoking reduces risk.

Summary

Oral health and overall health are closely linked. The biological justification of the associations is strong, and the epidemiological evidence is consistent, although causality (especially regarding cardiovascular endpoints) has not been definitively proven. Regular assessment of oral health and timely treatment of periodontitis is a sensible part of the comprehensive management of chronic diseases.

References

1. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30–44. PMID: 25534621.

2. Dominy SS, et al. Porphyromonas gingivalis in Alzheimer’s disease brains. Sci Adv. 2019;5(1):eaau3333. PMID: 30746447. (Correlation; causality debatable.)

3. Nakajima M, et al. Oral administration of P. gingivalis induces gut dysbiosis and systemic inflammation (animal models). PLoS One. 2015;10(7):e0134234. PMID: 26218067.

4. Kebschull M, et al. “Gum bug, leave my heart alone!” Epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis. J Dent Res. 2010;89(9):879–902. PMID: 20639510.

5. Han YW, Wang X. Mobile microbiome: oral bacteria in extra-oral infections and inflammation. J Dent Res. 2013;92(6):485–491. PMID: 23625375.

6. Preshaw PM, et al. Periodontitis and diabetes: a two-way relationship. Diabetologia. 2012;55(1):21–31. PMID: 22057194. (Diabetes ↑ periodontitis risk ~3×.)

7. Simpson TC, et al. Treatment of periodontitis for glycaemic control in people with diabetes mellitus. Cochrane Database Syst Rev. 2022; Issue 4:CD004714. (HbA1c decrease on average ~0.4%.)

8. Humphrey LL, et al. Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis. J Gen Intern Med. 2008;23(12):2079–2086. (RR range ~1.24–1.34.)

9. Fagundes NCF, et al. Periodontitis as a risk factor for stroke: systematic review and meta-analysis. Vasc Health Risk Manag. 2019;15:519–532.

10. CDC/AHA scientific statement on the use of hs-CRP in assessing cardiovascular risk; categories <1, 1–3, >3 mg/L. (e.g., Pearson TA et al., 2003; Ridker PM et al.)

11. Deng K, et al. Diagnostic accuracy of a point-of-care aMMP-8 test in periodontitis. J Periodont Res. 2021;56(6):1216–1228. (POCT utility; cutoff points vary.)