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Probiotics and Prebiotics for Oral Health
Wim TEUGHELSBelgium
Rank Health condition
Affected people
(millions) %
1 Untreated caries of permanent teeth 2,431 35.29
2 Tension-type headache 1,431 20.77
3 Migraine 1,012 14.70
4 Fungal skin diseases 985 14.30
5 Other skin and subcutaneous diseases 803 11.66
6 Severe periodontitis 743 10.79
7 Mild hearing loss 724 10.52
8 Acne vulgaris 646 9.38
9 Low back pain 632 9.17
10 Untreated caries of deciduous teeth 621 9.02
36 Severe tooth loss 158 2.3
Prevalence of
oral diseases
Periodontitis Caries/Tooth decay
Most prevelant health conditions in the world
Mic
rob
iolo
gy
Infla
mm
atio
n
Ae
tiolo
gy
of m
ajo
r ora
l dis
ea
se
s
1965
Oral biofilms & plaque related periodontal diseases
Bru
shin
g
An
tise
pti
cs a
nd
d
ete
rgen
ts
An
tib
ioti
cs
Solution
Fact: People leave dental biofilm after
brushing which is covered by a layer of
dead bacteria
MIC90 (µg/ml) Amoxicilin Spain vs. The Netherlands
32
256 256
0,38 1,5 0,0230
50
100
150
200
250
300
A.a Pi Fnbacterial species:
MIC
90
µg
/ml
Spain
The Netherlands
84 x
171 x 11130 x
MIC90 (µg/ml) Amoxicilin Spain vs. The Netherlands
32
256 256
0,38 1,5 0,0230
50
100
150
200
250
300
A.a Pi Fnbacterial species:
MIC
90
µg
/ml
Spain
The Netherlands
84 x
171 x 11130 x
33% R 33% R 20% R
Fact: Oral bacteria also become more
resistant to antibiotics when frequently
exposed to antibiotics
Fact: Antiseptics induce necrotrophy,
necrovirulence, resistance and can
increase antibiotic resistance
PRO
Evidence for probiotics in oral health is just emerging
Give it
time!
>30 studies
Probiotics & tooth decay
Author design n age vehicle time strain outcome test/ctl PF% NNTInfancyTaipele, 2013 RCT 106 0-2 pacifier/spoon 4y B. animalis BB-12 caries prevalence 31%/35% 11% 25Hasslöf, 2013 RCT 180 0-1 cereals 9y L. paracasei F19 caries prevalence 20%/26% 20% 17Stensson, 2014 RCT 188 0-1 drops 9y L. reuteri ATCC55730 caries prevalence 18%/42% 57% 4Toddlers & preschoolNäse, 2001 RCT 594 1-6 milk 7m L. rhamnosus GG caries prevalence 15%/19% 21% 25
164 3-4 milk 7m L. rhamnosus GG caries prevalence 10%/23% 56% 7Stecksén-B, 2009 CRCT 248 1-5 milk 21m L. rhamnosus LB21 +2.5 ppm F Δdmfs 0,3/1,6 48% 5H-Hajikand, 2015 RCT 138 2-3 tablets 12m Probiora Δds 0.2/0.8 49% 4Rodrigues, 2016 CRCT 261 2-3 milk 12m L. rhamnosus SP1 ΔIDAS(5-6) 9,7/24,3 61% 7AdultsPetersson, 2011 RCT 200 56-84 milk 15m L. rhamnosus LB21 rev rootcaries 54%/24% 55% 3
Jorgensen e.a. 2016
8 studies with true caries related outcome measure
preventive
fraction: 29%
Probiotics & tooth decay
Author design n age vehicle time strain outcome test/ctl PF% NNTInfancyTaipele, 2013 RCT 106 0-2 pacifier/spoon 4y B. animalis BB-12 caries prevalence 31%/35% 11% 25Hasslöf, 2013 RCT 180 0-1 cereals 9y L. paracasei F19 caries prevalence 20%/26% 20% 17Stensson, 2014 RCT 188 0-1 drops 9y L. reuteri ATCC55730 caries prevalence 18%/42% 57% 4Toddlers & preschoolNäse, 2001 RCT 594 1-6 milk 7m L. rhamnosus GG caries prevalence 15%/19% 21% 25
164 3-4 milk 7m L. rhamnosus GG caries prevalence 10%/23% 56% 7Stecksén-B, 2009 CRCT 248 1-5 milk 21m L. rhamnosus LB21 +2.5 ppm F Δdmfs 0,3/1,6 48% 5H-Hajikand, 2015 RCT 138 2-3 tablets 12m Probiora Δds 0.2/0.8 49% 4Rodrigues, 2016 CRCT 261 2-3 milk 12m L. rhamnosus SP1 ΔIDAS(5-6) 9,7/24,3 61% 7AdultsPetersson, 2011 RCT 200 56-84 milk 15m L. rhamnosus LB21 rev rootcaries 54%/24% 55% 3
8 studies with true caries related outcome measure
Jorgensen e.a. 2016
preventive
fraction: 29%
preventive
fraction: 47%
Probiotics & tooth decay
Author design n age vehicle time strain outcome test/ctl PF% NNTInfancyTaipele, 2013 RCT 106 0-2 pacifier/spoon 4y B. animalis BB-12 caries prevalence 31%/35% 11% 25Hasslöf, 2013 RCT 180 0-1 cereals 9y L. paracasei F19 caries prevalence 20%/26% 20% 17Stensson, 2014 RCT 188 0-1 drops 9y L. reuteri ATCC55730 caries prevalence 18%/42% 57% 4Toddlers & preschoolNäse, 2001 RCT 594 1-6 milk 7m L. rhamnosus GG caries prevalence 15%/19% 21% 25
164 3-4 milk 7m L. rhamnosus GG caries prevalence 10%/23% 56% 7Stecksén-B, 2009 CRCT 248 1-5 milk 21m L. rhamnosus LB21 +2.5 ppm F Δdmfs 0,3/1,6 48% 5H-Hajikand, 2015 RCT 138 2-3 tablets 12m Probiora Δds 0.2/0.8 49% 4Rodrigues, 2016 CRCT 261 2-3 milk 12m L. rhamnosus SP1 ΔIDAS(5-6) 9,7/24,3 61% 7AdultsPetersson, 2011 RCT 200 56-84 milk 15m L. rhamnosus LB21 rev rootcaries 54%/24% 55% 3
Jorgensen e.a. 2016
preventive
fraction: 29%
preventive
fraction: 47%
8 studies with true caries related outcome measure
Probiotics & tooth decay
8 studies with true caries related outcome measure
- 4 w 1 y 9 y
Control: placeboExperiment: L. reuteri ATCC 55730
Intervention: 5 drops / day
N=232
N=113
Total caries toothsurfaces
Plaque Index (%) Gingivitis index (%)
Probiotics & tooth decay
S. mutans numbers
Lo
wMedium High Lo
wMedium High
-70% *-19%
Probiotic
(n=18/746)
% o
f p
atie
nts
Control
(n=18/728)
+51% * +19% *
Probiotics & tooth decay
6th
Health Gingivitis
Health Gingivitis Periodontitis
Bleeding on probing
Probing pocket depth (PPD)
Boneloss
1 2 3 4 5 6 7 8 9 10 11 ...
mm
Health Gingivitis Periodontitis
Can probiotics prevent periodontitis?
Can probiotics prevent periodontitis?
Human studies10-40 years
Animal studies
Can probiotics prevent periodontitis?Relative bone level change Control Probiotic % reduction
Maekawa et al. L. brevis CD2 Mice Ligature -0,6 -0,22 -63%
Messora et al. B. subtilis Wistar rat Ligature -3,21 -2,38 -25%
Foureaux et al. B. subtilis Wistar rat Ligature -0,3 -0,12 -60%
Messora et al. B. subtilis + B. licheniformis Wistar rat Ligature -2,32 -1,07 -53%
Oliveira et al. B. animalis subsp. lactis Wistar rat Ligature -2,6 -1,6 -38%
Gatey et al. L. rhamnosus GG Mice Pg + Fn -0,06 -0,002 -96%
-56%
Irrespectively of mode of application(oral local or systemic) (Gatey et al 2018)
Ligature induced (foreign body): -48%Microbiologically induced: -96%
Can probiotics prevent periodontitis?
?
Evidence in Perio?
R/ ?
Heterogeneity
Optimism
Set-up Probiotic: Application: Outcome measure
- L. salivarius - tablets - PPD
- W. cibaria - chewing gum - GI
- L. reuteri - oral rinse - PI
- L. casei shirota - milk drink - BOP
- ……. - microbiology
Evidence in Perio?
>30 studies
+
+
+ ORPlacebo Probiotic
PPD
Baseline 21 days 3 months 6 months 12 months
Placebo 5.36±0.72 4.60±0.71 4.51±0.71 4.66±0.69 4.80±0.70
Probiotic 5.23±0.68 4.03±0.74* 3.80±0.75* 3.38±0.86* 3.49±0.87*
Teeth with PPD >= 5mm at 12 months
Baseline 12 months
Placebo 98,18% ± 4,07 89,34% ± 7,98
Probiotic 99,29% ± 1,6 29,91% ± 21,03 *-66.52%
Double blind placebo controlled 20 chronic periodontitis patients/armIntervention: SRP + placebo / probiotic(L. reuteri ATCC 55730 & PTA5289)lozenge 2/day for 3 weeksFollow-up: 12months
Study name Statistics for each study Difference in means and 95% CI
Difference Standard Lower Upper in means error Variance limit limit Z-Value p-Value
Teughels 2013 -0,020 0,075 0,006 -0,168 0,128 -0,266 0,790
Tekce 2015 -0,590 0,103 0,011 -0,791 -0,389 -5,740 0,000
Vivekananda -0,820 0,162 0,026 -1,137 -0,503 -5,071 0,000
-0,463 0,249 0,062 -0,951 0,025 -1,861 0,063
-1,00 -0,50 0,00 0,50 1,00
Favours probiotic Favours control
Meta Analysis
Evaluation copy
AZI: -0.32 [-0.53, -0.11]LDD: -0.28 [-0.45, -0.10]MET: -0.26 [-0.56, 0.04]MET+AMOX: -0.39 [-0.73, -0.05](Keestra et al 2014)WMD: -0,46 mm
Study name Statistics for each study Difference in means and 95% CI
Difference Standard Lower Upper in means error Variance limit limit Z-Value p-Value
Teughels 2013 -0,630 0,114 0,013 -0,854 -0,406 -5,520 0,000
Tekce 2015 -1,210 0,219 0,048 -1,640 -0,780 -5,521 0,000
-0,890 0,288 0,083 -1,455 -0,325 -3,085 0,002
-2,00 -1,00 0,00 1,00 2,00
Favours probiotic Favours control
Meta Analysis
Evaluation copy
WMD: -0,89 mm
PPD
PPD Deep AZI: -0.52 [-0.86, -0.18]]LDD: -0.62 [-0.84, -0.41]MET: -0.78 [-1.23, -0.33]MET+AMOX: -0.79 [-1.16, -0.42] (Keestra et al 2014)
How relevant are these differences?
Category Definition Placebo group Probiotic group
Low < 5 sites with PPD >4 2 (13.3%) 9 (60%)
Medium 5-8 sites with PPD > 4 3 (20%) 2 (13.3%)
High > 8 sites with PPD >4 10 (66.6%) 4 (26.6%)
Feres e.a. 2013
Risk for disease progression (Lang & Tonetti 2003)
How relevant are these differences?
Indirect, not yet direct
Category Definition Placebo group Probiotic group
None No teeth 2 (6%) 9 (26%)
Low 1-2 teeth 0 20 (57%)
Moderate-High >2 teeth 33 (94%) 6 (17%)
Need for surgery (Cionca et al. 2009 )
How relevant are these differences?
Tooth decay:49% preventive fraction
70% reduction in patients withhigh S. mutans counts
Oral Candida:48% reduction in patients with
high yeast counts
Gingivitis & periodontitis:> PPD reduction, CAL gain,
< need for surgery, Risk Disease Progression,
pathogens, Gi, Pi
Pregnancy gingivitis:58% ↓ Gi, 46% ↓ Pi
L. reuteri
Radiation mucositis:32% ↓ severe mucositis4x> without symptoms
Diabetes55% BOP reduction
Peri-implant diseases50% BOP reduction
Additional PPD reduction
Halitosis:15-60% reduction
Indirect causes
Probiotics in Dentistry
Are prebiotics an option?
Prebiotics
Oral health ≠ GI health?
3-5 min vs. 23 hours
Fast vs. Slow (fibers)
The quest for...
carbon
sources
nitrogen
sourcesP, S
sources
nutrient
supple
ments
peptide
nitrogen
sources
3/d, 3 min, 3d
7 9759
growth biofilm
11 9
27%
3%
3%
3%
The quest for...
Fiber prebiotic?
-1,20 mm +/- 0,14 -2,10 mm +/- 0,36 -1,78 mm +/- 0,35
-36%
N= 18 Wistar rats6: healthy 6: periodontitis induction (2 weeks) + ß-glucan 30mg/kg/day (4 weeks) via gavage6: periodontitis induction (2 weeks)
GI health – Oral health connection
Specific probiotics can help in the prevention and treatment of
oral diseases
Prebiotics are under development (very limited evidence)
When designing (clinical) trials, also consider oral health
