Table 1: The effect of interventions in the included studies.

Study Study Design No. of Participants Intervention/s Follow up Period Type of Sample & (Plat-Form) Outcomes (Effect size) Interpretation
Clinical Microbiological
     I. The effect of non-surgical periodontal treatment
(Jünemann et al., 2012) [44] RCT 4 I*: Mechanical debridement + 500 mg Amoxicillin + 400 mg Metronidazole
VS
C*: Mechanical debridement + placebo
2 months Subgingival (Ion Torrent) Mean diff.
%PPD>7mm*= -0.8
%BOP*=-1
%PI*=4.5
Control (before and after)
%PPD*=-18.7
%BOP*= -55
%PI*=-46
Mean diff.
ACE= -58.5
Shannon=-0.48
Simpson=0.025
Evenness= -0.04
Control
ACE=28.5
Shannon=0.29
Simpson= -0.03
Evenness=0.035
Clinical and microbiological results favor I*
C* alone improves clinical but not microbiological results
(Hagenfeld et al., 2018) [41] RCT 96 I*: Mechanical debridement + 500 mg Amoxicillin + 400 mg Metronidazole
VS
Mechanical debridement. + placebo
2 months Subgingival (Illumina MiSeq) Mean diff.
%PPD5mm*= -2.7
%BOP= -4.3
%RAL1.3mm*= 0.1
Control
%PPD5= 7.5
%BOP=16.4
Mean diff.
Richness= -14.91
Evenness= 0
Diversity= -0.1
Dissimilarity= 0.04
Contol
Richness= -4.41
Evenness= 0
Diversity= 0.02
Dissimilarity=
-0.01
Clinical and microbiological results favor I*
C* alone improves microbiological but not clinical results
(Chang, 2012) [45] Before and after 4 Scaling and root planning + oral hygiene instruct. Baseline, 4-6 weeks Subgingival (Shotgun: Illumina GAIIx) Mean difference
GI*=-1.3
PD*= -2 mm
GR*= 1.3mm
CAL*= -1.5 mm
Descriptive data only I* improves the clinical results and causes a shift in the subgingival microbial community
(Shi et al., 2015) [46] Before and after 12 Scaling and root planning + oral hygiene instruct. Baseline, week 4 and 19 Subgingival (Shotgun: Illumina GAIIx) Not mentioned;
The study only included the clinically resolved cases
No numbers reported (diversity in resolved< diseased) According to descriptive data, I* improves the microbiological results
(Yamanaka et al., 2012) [47] Before and after 19 Scaling and root planning + oral hygiene instruct. Baseline and 2 years Saliva and supragingival (pyrosequencing) Mean diff. between
% of pockets>7mm= -6.98%
Mean diff.
Chao I= -211
ACE=-214
Shannon=- 0.3
Intervention improves clinical and microbiological results
     II. The effect of other interventions (Miscellaneous)
(Califf et al., 2017) [48] Non-RCT 34 I*: 0.25% sodium hypochlorite rinse
VS
C*: 15 ml of water rinse
Baseline, day 14, month 3 Supra and subgingival plaque (Illumina MiSeq) Not stated to be an outcome for the study No numbers reported. According to descriptive data, I* causes a shift in the plaque microbial community
(Hagenfeld et al., 2019) [40] RCT 41 I*: zinc-substituted carbonated hydroxyapatite dentifrice
VS
C*: dentifrice containing an amine fluoride/stannous fluoride
Baseline, week 4 and 12 Supra and subgingival plaque (Illumina MiSeq) Mean diff
PFR*=2.3%
PCR*=2.6%
GI*=-0.1
BOP*=0.9%
PPD*=-0.1 mm
GR*=0.2 mm
AL*=0.1mm
No noticeable difference between the 2 groups C* provides better clinical results than I* and both show similar microbiological effects.
(Nakano et al., 2017) [43] RCT 46 tablets contain 80 mg of LF+LPO powder (Lactoferrin + lactoperoxidase) VS placebo Baseline, week 4 and week 8 Tongue coating and supragingival plaque
(Illumina MiSeq)
No postoperative numbers reported No postoperative numbers reported (lower diversity in I* than placebo) I* causes shift in the plaque microbial community lowering the diversity
(Queiroz et al., 2017) [42] RCT 41 with furcation involvement Bone Vs EMD* VS Bone + EMD Baseline, 3 and 6 months Subgingival plaque from the furcation defect
(pyrosequencing)
No data about intervention or control No numbers reported -

* %PPD>7 mm, percentage of tooth sites with pockets>7mm ; %PPD 5 mm, percentage of tooth sites with pockets≥5mm ; %BOP, percentage of tooth sites with bleeding on probing ; %PI= ; %RAL1.3 mm, percentage of tooth sites with further relative attachment loss≥1.3mm ; AL, attachment level; BOP, Bleeding on probing; C, Control; CAL, clinical attachment loss; EMD, Enamel Matrix Derivatives; GI, gingival index ; GR., Gingival recession ; I, intervention; PCR, O’Leary's plaque control record; PD, probing depth; PFR, de novo plaque formation rate; PPD, probing pocket depth.