Resistance and resilience to experimental gingivitis: a systematic scoping review

Abstract

Background This systematic scoping review aimed to identify changes in biomarkers of microbiological, immunological and biochemical origin during experimental gingivitis (EG) studies that might indicate resistance and resilience. Methods The term ‘experimental gingivitis’ was run in PubMed from inception to April 11th, 2018. From the 411 studies retrieved, 22 studies were included for this review. Results Studies reporting data on biomarker changes during and after full mouth EG trial were included. Two studies reported findings on changes in biomarkers of microbiological, 12 on immunological and eight on biochemical origin. Changes were reported in the induction phase, and occasionally in the resolution phase. The microbiological composition of both supragingival and subgingival dental plaque changed over the course of EG to a more pathogenic direction, but showed a shift back to a more normal composition. This indicates resilience of the oral microbiome. For immunological biomarkers, it was challenging to retrieve a robust pattern of changes across multiple studies. IL-1β and IL-6 in saliva and in gingival crevicular fluid increased during induction phase and returned in the resolution phase below baseline values. The biochemical parameters cystatin-SN, cystatin-S and lactoferrin in saliva were increased at the end of induction phase, however also here no clear pattern emerged based on all available studies. Conclusions More research is needed to investigate which microbiological, immunological, and biochemical biomarkers can be useful for future investigations into the resistance and resilience of the oral cavity to experimental gingivitis.

Maintaining homeostatic control of periodontal epithelial tissue

“…Clinical studies investigating inflammatory changes over time in healthy patients abstaining from oral hygiene reported increases in gingival inflammation and microbial diversity and load that can occur within days 3537 . Reduction of microbial load by administration of oral hygiene or antibiotics reverses clinical signs of disease, demonstrating that the junctional epithelium has the ability to regenerate and restore this delicate balance of homeostasis 35,38,41 . However, the mechanisms that are in play to regulate this precise balance still require further characterization.…”

“…Neutrophils, which are part of the innate immune system, provide a rapid, broad‐spectrum response against bacteria by phagocytosis and/or release of superoxides and peroxides. Improper regulation of these immune cells is detrimental to periodontal health 41‐44 . This is most evident in patients with the inability to regulate proper neutrophil numbers (neutropenia), recruitment (Chediak‐Higashi syndrome and Papillon‐Lefèvre syndrome), or adhesion (congenital or induced neutrophil deficiencies in leukocyte adhesion deficiency type I, type II, and type III), or, conversely, with the failure to downregulate neutrophil transit, resulting in uncontrolled neutrophil recruitment or prolonged exposure, which all lead to increases in alveolar bone loss 41,45‐50 .…”

“…Improper regulation of these immune cells is detrimental to periodontal health 41‐44 . This is most evident in patients with the inability to regulate proper neutrophil numbers (neutropenia), recruitment (Chediak‐Higashi syndrome and Papillon‐Lefèvre syndrome), or adhesion (congenital or induced neutrophil deficiencies in leukocyte adhesion deficiency type I, type II, and type III), or, conversely, with the failure to downregulate neutrophil transit, resulting in uncontrolled neutrophil recruitment or prolonged exposure, which all lead to increases in alveolar bone loss 41,45‐50 . Furthermore, abnormalities in neutrophil lifespan, activation, and function, such as with decreased phagocytosis or increased superoxide production, are also associated with periodontal disease 51‐53 .…”

Future directions for studying resilience of the oral ecosystem

“…47 We have recently reviewed the evidence for resistance and resilience to experimental gingivitis. 35 Fluctuations of immunological, biochemical and microbiological biomarkers were identified throughout different phases and challenges to the oral cavity. In some cases, trends in biomarkers appeared to correlate with resilience.…”

“…Resistance and resilience are temporal concepts and cannot be fully understood with cross-sectional studies. However, with the exception of the well-characterised experimental gingivitis model, 35 relatively few studies have investigated longitudinal changes in the oral microbiome or in host inflammatory mediators through the course of cariogenic or gingivitis/periodontitis challenges. As a result, there are currently no strong biomarkers that can classify different levels of resistance or resilience, or that can explain the mechanistic basis of these differences.…”