Low Biofilm Lysine Content in Refractory Chronic Periodontitis

• Autores: Martin Levine, Zsolt Lohinai, Ricardo P. Teles
• Localización: Journal of periodontology, ISSN 0022-3492, Vol. 88, Nº. 2, 2017, págs. 181-189
• Idioma: inglés
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• Resumen

  • Background: Chronic periodontitis is controlled without antibiotics by scaling and root planing (SRP) to remove dental biofilm. It has been previously reported that the epithelial barrier to bacterial proinflammatory products is impaired when biofilm lysine falls below the minimal content of normal blood plasma. Aims were to examine whether being refractory and requiring antibiotics to supplement SRP were associated with low biofilm lysine contents.

    Methods: Sixteen patients with periodontitis and six periodontally healthy volunteers (HVs) (respective mean ages: 57 ± 6 and 36 ± 8 years) were examined. Patients with periodontitis received SRP and surgery, and HVs received prophylaxis. At quarterly maintenance or prophylaxis visits during the subsequent year, therapeutic response was good (GR, n = 9) or poor (PR, n = 7; including five cigarette smokers). Biofilm cadaverine, lysine, and other amino acid (AA) contents were determined by liquid chromatography. Cadaverine mole fraction of lysine plus cadaverine (CF) indicated biofilm lysine decarboxylase activity.

    Results: Biofilm lysine was 0.19 ± 0.10 and 0.20 ± 0.09 μmol/mg in GRs and HVs, but 0.07 ± 0.03 μmol/mg in PRs (Kruskal–Wallis: P <0.01). All AAs were depleted in biofilm from smokers, but only lysine was depleted in biofilm from non-smokers. CF was inversely associated with clinical attachment level (CAL) at baseline before therapy in all patients (R2 = 0.28, P <0.01) and with CAL change after therapy in GR (R2 = 0.49, P <0.05). Lysine and cadaverine contents discriminated PRs from GRs and HVs (Wilks’ λ = 0.499, P <0.012).

    Conclusions: Refractory responses requiring antibiotic therapy result from smoking and/or microbial infections that starve the biofilm and epithelial attachment of lysine. Biofilm CF is associated with periodontitis severity pretherapy and extent of therapeutic response post-therapy.

    Periodontal disease is a bacterially induced, destructive inflammatory lesion of the periodontium. Aggressive periodontitis (AgP) affects <0.1% of the population in the United States, whereas chronic periodontitis (CP) affects 46% of adults in the United States aged ≥30 years1 and correlates with increased susceptibility to coronary heart disease,2 diabetes,3 and perhaps some other diseases. Antibiotic therapy (amoxicillin and metronidazole) is the standard therapy for AgP,4,5 but most patients with CP are successfully treated without antibiotics.6 Indeed, concerns about the ever-increasing development of antimicrobial resistance makes it imperative that a more objective method of prescribing antimicrobials for treating CP is developed.7 Up to 30% of patients with moderate CP respond poorly to therapy (i.e., refractory).8 About 70% of current smokers are refractory to therapy and account for at least half of all the refractory patients.9,10 A better understanding of why smoking and other factors cause a poor response to therapy is necessary for developing a scientific rationale underlying the use of adjunctive antibiotics to treat CP.

    CP begins as gingival inflammation (gingivitis) in which the coronal tooth–soft tissue attachment, the gingiva, becomes red and inflamed and may bleed on gentle probing. In a healthy oral cavity, gingivitis is initiated by dental biofilms composed of the commensal salivary microbiota. In the absence of oral hygiene, the biofilms thicken, bacteria become more diverse, and gingival crevicular fluid (GCF) increases at the tooth–soft-tissue junction where it promotes growth of a disease-associated (successor) microbiota11 associated with established gingivitis and CP12 (see supplementary Fig. 1 in online Journal of Periodontology).

    Authors ML and ZL have developed a model which explains gingivitis development ab initio in experimental human and canine gingivitis models.13-15 If gingivally healthy or periodontally treated individuals restrict their oral hygiene for a week, Eikenella corrodens increases16 along with an enzyme, lysine decarboxylase (LDC), in 82% of isolates.17 At the base of gingival sulci, dentally attached cells of junctional epithelium must divide to maintain a basal laminar attachment. The attached cells have no underlying capillaries and are nourished by a GCF resembling interstitial fluid that passes through the epithelium. Lysine in the GCF is essential for cell division and epithelial attachment because it cannot be replaced by de novo epithelial cell synthesis.13,14 When oral hygiene stops, E. corrodens and its LDC increase at the base of gingival sulci (see supplementary Fig. 2 in online Journal of Periodontology). LDC converts the lysine in GCF to cadaverine, causing dentally attached cells to lose their ability to divide and remain attached. The dental epithelial attachment becomes permeable to biofilm components. GCF changes from an interstitial fluid containing only traces of protein to an inflammatory exudate which increases in protein content and promotes development of the successor microbiota.13 Despite therapy, cigarette smoking or bacterial metabolism may reduce biofilm lysine content in addition to LDC. Aims were therefore to examine whether being refractory and requiring antibiotics to supplement SRP were associated with low biofilm lysine contents.