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Table 1 Overview of included studies: description of study characteristics and extracted data, stratifies by microbiological (A), immunological (B) and biochemical (C) outcomes

From: Resistance and resilience to experimental gingivitis: a systematic scoping review

First author, yearreference Study population Design set up Parameters Results resilience
A. Microbiological outcomes
 Lie, 1998 [6] N = 25
Age: 19–27 years, mean: 22
Sex: M: 12, F:13
Groups: 1 group non-dental university students
Ethnicity: NR
Smoking: 11 (M:6; F:5)
Average cigarettes: 15.6 a day
General health: Good general health
Oral health: 24 teeth, > 30% bleeding on probing, pockets < 5 mm.
Pre-trial phase:
Length: NR
Treatment: OHI, PP
Induction phase:
Length: 14 days
Treatment: PP at the end
Resolution phase: N/A
Samples: supragingival plaque, approximal plaque, subgingival plaque, tongue scrape
- Total CFU
- P. micros
- Streptococcus spp.
- A. actinomycetemcomitans
- C. rectus
- F. nucleatum
- P. intermedia
- Actinomyces spp.
Supragingival plaque
No difference found in groups and over time in total CFU, P. micros, Streptococcus spp. Actinomyces spp. and F. nucleatum, P. intermedia increased from day 0 to day 14 in non-smokers group. C. rectus increased in both groups.
Subgingival plaque
No difference was found over time and between P. micros, Streptococcus spp., A. actinomycetemcomitans, C. rectus, F. nucleatum
groups in abundance.
Total CFU in smokers was at day 14 higher compared to baseline. Actinomyces spp. and P. intermedia increased significantly over time in both groups.
Approximal plaque:
Total CFU, A. actinomycetemcomitans, Actinomyces spp., C. rectus (in smokers) and F. nucelatum (in non-smokers), P. micros, streptococci spp. did not change over time.
Actinomyces spp. and C. rectus increased over time in non-smokers group and F. nucleatum in smokers group.
 Salvi, 2005 [7] N = 22
Age: mean 24.7 (2.2 SD) years
Sex: M:7, F:15
Groups: smokers (N = 11) and control group of non-smokers (N = 11) all students.
Ethnicity: NR
Smoking: 11, > 5 years of smoking
General health: No relevant medical conditions, general good health
Oral health: > 24 permanent teeth, pockets < 4 mm
Pre-trial phase:
Length: 21 days
Treatment: PP and OHI
Induction phase:
Length: 21 days
Treatment: none
Resolution phase:
Length: 14 days
Treatment: OHI, PP
Sample: subgingival plaque
- P. gingivalis
- T. denticola
- T. forsythia
Bacteria in smokers and non-smokers did not differ over time. At day 35 smokers had fewer bacteria compared to day 21.
B. Immunological outcomes
 Belstrom, 2017 [9] N = 29
Age: 22–29 years
Sex: M: 5, F:24
Groups: dental students
Ethnicity: NR
Smoking: non-smokers
General health: Systemically healthy
Oral health: No active caries, no gingivitis or periodontitis, no hyposalivation or medication use.
Pre-trial phase:
Length: none
Treatment: NA
Induction phase:
Length: 10 days
Treatment: none
Resolution phase:
Length: 14 days
Treatment: none
Samples: stimulated saliva
- IL-1β
- IL-8
- MCP-1
- VEGF
IL-1β, IL-8, MCP-1, and VEGF levels all reduced during induction phase compared to baseline levels. And IL-8 remained low after resolution phase.
 Brecx, 1988 [10] N = 8
Age: 22–26 years
Sex: NR
Groups: dental students
Ethnicity: NR
Smoking: NR
General health: NR
Oral health: NR
Pre-trial phase:
Length: 14 days
Treatment: PP
Induction phase:
Length: 21 days
Treatment: none
Resolution phase:
Length: 8 days
Samples: gingival biopsy
- Lymphocytes
- Macrophages
- PMNs
- Plasma cells
Levels of lymphocytes, plasma cells and macrophages did not change at day 8 of the resolution phase compared to end of EG, except PMNs: they increased significantly at day 8 (18.1% at end of EG, 21.9% at day 8 of resolution
 Giannopoulou, 2003 [11] N = 22
Age: 19–33 years, mean 26
Sex: M: 14, F: 8
Groups: dental students, 2 groups non-smokers and smokers
Ethnicity: NR
Smoking: N = 10
General health: Systemically healthy
Oral health: Smokers > 10 cigarettes a day, > 24 permanent teeth, GI < 1
Pre-trial phase:
Length: 12 days
Treatment: PP, OHI
Induction phase:
Length: 10 days
Treatment: PP, OHI
Resolution phase: N/A
Samples: GCF
- IL-1β
- IL-4
- IL-8
IL-1β increased significantly in the induction phase in both smokers and non-smokers.
IL-4 at baseline is significantly lower in smokers compared to non-smokers and does not change over time. In non-smokers IL-4 decreases significantly over time and stays higher compared to smokers.
IL-8 levels at baseline is significantly higher compared to non-smokers, this applies also at day 10. In both smokers as non-smokers the levels of IL-8 increase significantly.
 Heasman, 1992 [12] N = 7
Age: 18–21 year
Sex: NR
Groups: NR
Ethnicity: NR
Smoking: NR
General health: NR
Oral health: > 20 permanent teeth, < 3 mm pocket depth, no bone loss
Pre-trial phase:
Length: 7 days
Treatment: PP
Induction phase:
Length: 28 days
Treatment: PP
Resolution phase: N/A
Samples: GCF
- IL-1B
- LTB4
- PGE2
- TxB2
IL-1B increased over time during the induction phase compared to baseline. LTB4 levels differed significantly only in 7 and 28 days, in between the levels stay the same as baseline values. PGE2 and TxB2 values only changed compared to baseline after 28 days, before that the levels stay the same as at baseline.
 Kinane, 1992 [13] N = 12
Age: 20–21 years
Sex: M: 8, F: 4
Groups: dental students
Ethnicity: NR
Smoking: NR
General health: Unremarkable medical history
Oral health: >  26 permanent teeth, healthy gingiva, < 4 mm pocket depth, no attachment loss
Pre-trial phase:
Length: 8 weeks
Treatment: monitoring oral health
Induction phase:
Length: 21 days
Treatment: PP
Resolution phase:
Length: 14 days
Treatment: none
Samples: GCF
- IL-1 IL-1 levels strongly increase from baseline to day 4 and stay at the same levels until day 14. The IL-1 levels return back to baseline levels at the end of the induction phase.
 Leishman, 2013 [14] N = 8
Age: 25.5 (7.1 SD) years
Sex: M: 0, F: 8
Groups: university students
Ethnicity: NR
Smoking: none
General health: Systemically healthy, non-pregnant and no use of antibiotics
Oral health: No history of periodontal disease
Pre-trial phase: N/A
Induction phase:
Length: 21 days
Treatment: PP and Oral B toothbrush
Resolution phase:
Length: 14 days
Treatment: none
Samples: GCF, saliva, blood plasma
- IL-1β
- IL-2
- IL-4
- IL-5
- IL-6
- IL-10
- IFN-γ
- sICAM-1
- TNF-α
GCF sample:
IL-1β significantly decreases after 35 days. IL-2 increases from baseline to day 21 and decreases 10 fold at 35 days.
TNF-α decreased in resolution phase and sICAM-1 was significantly higher at day 35 compared to day 14. IL-4, IL-5, IL-10, IL-12 and IF-γ values stayed the same over time.
Saliva sample:
Only IL-1β significantly decreased at day 35 compared to day 21. Other parameters did not change significantly.
Plasma sample:
Only sICAM-1 values changed significantly over time and increased from baseline to day 35. However the values between day 21 and 35 were not significantly different.
 Lie, 2002 [15] N = 25
Age: 19–27 mean 22 year
Sex: M: 12, F:13
Groups: 1, non-dental university students
Ethnicity: NR
Smoking: N = 11
General health: Good general health
Oral health: > 24 permanent teeth, < 4 mm pocket depth, no attachment loss
Pre-trial phase:
Length: NR
Treatment: PP
Induction phase:
Length: 14 days
Treatment: PP
Resolution phase: N/A
Samples: stimulated saliva
- Total parotid salivary IgA No change in salivary-IgA over time or difference between groups.
 Norman, 1979 [16] N = 10
Age: NR
Sex: Male
Groups: dental students
Ethnicity: NR
Smoking: none
General health: Healthy
Oral health: No periodontitis
Pre-trial phase:
Length: NR
Treatment: PP
Induction phase:
Length: 21 days
Treatment: PP
Resolution phase: N/A
Samples: Blood and GCF
- IgA
- IgM
- IgG
IgG, IgM, IgA, showed no significant changes during the induction phase.
 Reuland-Bosma, 1987 [17] N = 16
Age: NR
Sex: NR
Groups: 2, 1 down syndrome children, 1 healthy control children.
Ethnicity: NR
Smoking: none
General health: NR
Oral health: NR
Pre-trial phase: N/A
Induction phase:
Length: 21 days
Treatment: none
Resolution phase: N/A
Samples: gingival biopsies
- Leukocytes
- PMNs
Number of PMNs and leukocytes did not change over time in the induction phase compared to baseline.
 Seemann, 2004 [18] N = 14
Age: 22–37, mean 27 years
Sex: M:14, F: 0
Groups: 1
Ethnicity: NR
Smoking: none
General health: Clinically healthy
Oral health: > 24 teeth, pockets depth < 4 mm, no active caries, good general health
Pre-trial phase:
Length: 2 days
Treatment: none
Induction phase:
Length: 12 days
Treatment: PP
Resolution phase: N/A
Samples: (un)stimulated saliva
- Parotid IgA concentration
- Parotid IgA secretion
- SM/SL IgA concentration
- SM/SL IgA secretion
Parotid IgA concentration, stayed the same during the trial. Parotid IgA secretion in stimulated saliva increased significantly from baseline to end of induction phase.
SM/SL IgA concentration and secretion remained stable during the experiment.
 Tsalikis, 2010 [19] N = 10
Age: 20–22 (N = 5) and 61–65 years (N = 5)
Sex: M:6, F: 4
Groups: 2, young adults and old adults
Ethnicity: Caucasians
Smoking: none
General health: Clinically healthy
Oral health: healthy periodontum, no bone loss, > 20 permanent teeth, attachment loss < 3 mm, bleeding on probing < 10%, plaque index < 20%
Pre-trial phase: N/A
Induction phase:
Length: 21 days
Treatment: none
Resolution phase:
Length: 7 days
Treatment: PP
Samples: GCF
- IL-6
- IL-8
- TNF- α
Young group: TNF- α did not change over time. IL-6 and IL-8 increased from baseline to induction and to resolution phase.
Old group: TNF- α increased from baseline to end of induction phase, and IL-6 from end induction phase to end of resolution phase.
 Wahaidi, 2009 [20] N = 156
Age: 18–31 years
Sex: NR
Groups: non smoking
Ethnicity: NR
Smoking: none
General health: healthy
Oral health: No periodontitis, < 4 mm probing depth, no caries
Pre-trial phase:
Length: 21 days
Treatment: OHI
Induction phase:
Length: 21 days
Treatment: PP, OHI
Resolution phase:
Length: 21 days
Treatment: none
Samples: peripheral blood
- White blood cells
- PMNs
No significant change in either parameter over time.
 Zhou, 2012 [21] N = 11
Age: years
Sex: M: 11, F: 0
Groups: 1 group non-smoking dental students
Ethnicity: NR
Smoking: none
General health: Unremarkable medical history
Oral health: No periodontal disease, > 24 permanent teeth, healthy gingiva, good oral hygiene
Pre-trial phase: N/A
Induction phase:
Length: 21 days
Treatment: none
Resolution phase:
Length: 7 days
Treatment: none
Samples: unstimulated whole saliva
- IL-6
- IL-1β
IL-6 showed increase at day 21 and returned to baseline values during the resolution phase.
IL-1 β was significantly higher at day 14 and 21 compared to baseline, and returns to baseline values in resolution phase.
C. Biochemical outcomes
 Aboodi, 2015 [8] N = 5
Age: 20–36 year
Sex: M:2, F:3
Groups: NR
Ethnicity: NR
Smoking: none
General health: Systemically healthy
Oral health: Periodontally healthy
Pre-trial phase:
Length: 7 days
Treatment: PP, OHI
Induction phase:
Length: 21 days
Treatment: none
Resolution phase:
Length: 14 days
Treatment: OHI, PP
Sample: whole saliva
Proteome (fold change):
- SPARC-like protein 1 (2.10)
- Calmodulin-like protein 3 (2.11)
- Mucin-6 (2.13)
- Cystatin-S (2.14)
- LOC349136 (2.18)
- Tetratricopeptide repeat protein 28 (2.20)
- Androgen receptor (2.21)
- Serine 13 (2.21)
- Carbonic anhydrase 6 (2.23)
- Kinesin-like protein KIF3B (2.23)
adenocarcinoma factor (2.25)
- Thioredoxin (2.29)
- cDNA FLJ38275 (2.31)
- Apolipoprotein A-1 (2.32)
- Pancreatic - Albumin (2.33)
- Cystatin-SN (2.33)
- OLIG2 (2.47)
- Vitamine D-binding protein (2.78)
- IG kappa chain C region (2.87)
- G-protein r98 (3.41)
- Lactoferrin (a.k.a. lactotransferrin) (3.50)
- Beta-globin (3.75)
- Anenxin A1 (4.15)
- KIAA1539 (4.72)
- Collagen alpha-1 (7.35)
All reported proteins changed over time and have a fold change > 2.
 Adonogianaki, 1994 [22] N = 6
Age: 22–23 year
Sex: M:5, F:1
Groups: dental students
Ethnicity: NR
Smoking: NR
General health: NR
Oral health: < 3 mm pocket depth, no periodontal attachment loss
Pre-trial phase:
Length: 10 days
Treatment: PP, OHI
Induction phase:
Length: 21 days
Treatment: none
Resolution phase:
Length: 14 days
Treatment: none
Samples: GCF
- Alpha2-macroglobulin
- Alpha1-antitrypsin
- Transferrin
- Lactoferrin
Alpha1-antitrypsin, Alpha2-macroglobulin and transferrin increased during the induction phase and stayed elevated in the resolution phase. Lactoferrin increased also during the induction phase, but dropped again almost to baseline levels during the resolution phase.
 Lie, 2001 [23] N = 25
Age: 17–27 mean 22 years
Sex: NR
Groups: 2 groups, non-smokers and smokers
Ethnicity: NR
Smoking: 11
General health: Good general health
Oral health: having gingivitis > 30% bleeding upon probing, < 5 mm of pockets, absence of approximal attachment loss. When treated in the pre-trial phase, patients with < 20% approximal bleeding sites entered the trial
Pre-trial phase
Length: NR
Treatment: OHI and PP
Induction phase:
Length: 14 days
Treatment: none
Resolution phase: N/A
Samples: saliva
- Total protein (mg/ml)
- Cystatin activity (units/ml)
- Cystatin C (μg/ml)
- Output cystatin activity (units/min)
- Output cystatin C (μg/min)
Mean protein values remained stable over time.
Cystatin activity significantly decreased at day 14 compared to baseline in smokers.
Cystatin C was at day 14 significantly higher in non-smokers, and decreased during induction in smokers.
Output cystatin activity was at day 14 higher in non-smokers.
Output cystatin C decreased during induction in non-smokers and was significantly higher in smokers at day 14
 Norman, 1979 [16] N = 10
Age: NR
Sex: M: 10, F:0
Groups: dental students
Ethnicity: NR
Smoking: NR
General health: NR
Oral health: periodontally healthy
Pre-trial phase:
Length: NR
Treatment: PP
Induction phase:
Length: 21 days
Treatment: PP
Resolution phase: N/A
Samples: Blood and GCF
- Alpha-antitrypsin
- C4
- C3
- CH50
- Factor B
- Transferrin
C3, Factor B, Alpha-antitrypsin and transferrin showed no significant changes during the induction phase. CH50 and C4 increased significantly at day 21 compared to baseline values.
 Ozdemir, 2009 [24] N = 12
Age: 19–21 years
Sex: M: 12; F:0
Groups: dental students
Ethnicity: NR
Smoking: none
General health: NR
Oral Health: > 24 permanent teeth, systemic healthy, < 4 mm pocket depth, no attachment loss
Pre-trial phase:
Length: 14 days
Treatment: OHI, PP
Induction phase:
Length: 14 days
Treatment: OHI, PP
Resolution phase:
Length: 21 days
Treatment: none
Samples: GCF, peripheral blood
- Lactoferrin Lactoferrin in GCF and blood increased during the induction phase and returned to baseline in the resolution phase.
 Que, 2004 [25] N = 15
Age: 18–30 years
Sex: M: 6, F: 9
Groups: NR
Ethnicity: NR
Smoking: none
General health: Systemically healthy no NSAIDs use.
Oral health:  < 5 mm pocket depth, no attachment loss
Pre-trial phase:
Length: 11 days
Treatment: PP and OHI
Induction phase:
Length: 10 days
Treatment: PP
Resolution phase: N/A
Samples: GCF
- Total protein (ng/site)
- Calprotectin (MRP8/14) (ng/site)
- subunit MRP 8 (ng/site)
- subunit MRP 14 (ng/site)
Total protein, calprotectin, MRP 8 and 14 did not change from baseline to day 10. However 1 day after cleaning this did increase significantly.
 Siegel, 2007 [24] N = 14
Age: 18–30 and 46–77 years
Sex: M: 9, F: 5
Groups: 2 groups, 18–30 year old subject and 47–77 year old.
Ethnicity: NR
Smoking: none
General health:
No systemic diseases
Oral health:
< 3 mm pocket depth, no bleeding on probing, non-susceptible for periodontitis, > 20 permanent teeth, no systemic disease
Pre-trial phase:
Length: 21 days
Treatment: OHI and PP
Induction phase:
Length: 14 days
Treatment: PP
Resolution phase: N/A
Samples: gingival biopsy
- Cyclooxygenase − 1
- Cyclooxygenase − 2- Cyclooxygenase − 3
- Microsomal prostaglandin e synthese-1
Cyclooxygenase − 1 expression in Langerhans’cells increased in both study groups but was not significant.
Cyclooxygenase − 2 expression in basal epithelial cells were significantly lower in the older age group.
Cyclooxygenase − 3 was not detected in tissue samples.
Microsomal prostaglandin E synthese-1 was detected in epithelial, endothelial and fibroblast-like connective tissue cells, however no significant difference was found between ages.
 Uitto, 1996 [26] N = 12
Age: NR
Sex: NR
Groups: 2 groups, student hygienists and healthy adults
Ethnicity: NR
Smoking: NR
General health: NR
Oral health:
healthy periodontium
Pre-trial phase: N/A
Induction phase:
Length: 10 days
Treatment: none
Resolution phase: N/A
Samples: saliva samples; water rinses
- Elastase No significant changes in salivary elastase levels during the experiment.
 Zhou, 2012 [21] N = 11
Age: 21–22 years
Sex: M: 11, F: 0
Groups: 1 group non-smoking dental students
Ethnicity: NR
Smoking: none
General health:
Unremarkable medical history
Oral health:
No periodontal disease, > 24 permanent teeth, healthy gingiva, good oral hygiene
Pre-trial phase: N/A
Induction phase:
Length: 21 days
Treatment: none
Resolution phase:
Length: 7 days
Treatment: none
Samples: unstimulated whole saliva
- Calprotectin
- Elastase activity
Calprotectin showed only change at day 21,and returned to baseline levels. Elastase activity was higher in the induction phase compared to resolution phase.
  1. Abbreviations: M male, F female, NR not reported, OHI oral hygiene instruction, PP professional prophylaxis, N/A not applicable, OH oral hygiene, GCF gingival crevicular fluid, SD standard deviation, GI gingival index, IL- interleukin, PMN polymorphonuclear neutrophils, TNF tumour necrosis factor, mm millimetres, VEGF vascular endothelial growth factor