A presentation with bite. Improving oral health in an ...€¦ · Gingivitis and Periodontitis ... presentation at Vitafoods Europe, Geneva, 2017 12. Traditional treatment of periodontitis

Anders Henriksson, PhD

Principal Application Specialist

July 10, 2019

A presentation with bite. Improving oral

health in an ageing population

Why Oral Health ?

2

A global issue

Mean percent of Community Periodontal Index (CPI)* scores in 35-44 year olds

by global World Health Organisation (WHO) offices

* CPI scores are defined by WHO protocol and is a standardized means of dental disease measurement used to compare reports

Modified from Petersen and Ogawa (2005) J Periodontol 76 (12):2187-2193

3

8 out of 10 people aged

35 years and over

suffer some kind of

gum complaint

Less than 10% of 35-44 year olds

have healthy gums

100 %

80 %

60 %

40 %

20 %

0 %

CPI 0 - healthy periodontal

conditions

CPI 1 - gingival bleeding

CPI 2 - gingival and calculus

bleeding

CPI 3 - shallow periodontal

pockets (4-5mm)

CPI 4 - deep periodontal

pockets (≥ 6mm)

Africa Americas Eastern

Mediterranean

Europe South

East Asia

Western

Pacific

Gingivitis and Periodontitis

▪ The oral cavity is home to more

than 700 different bacterial

species

▪ Biofilms are formed by bacterial

communities which reside in

saliva-covered soft and hard

tissues

▪ Oral biofilms are associated

with infectious diseases such

as tooth decay (caries) and

periodontal disease

Gingivitis

Gingivitis can cause dusky red, swollen,

tender gums that bleed easily, especially

when you brush your teeth.

Healthy gums Severe periodontitis(more than 6 mm pockets)

- Extensive bone and

tissue loss, teeth can

become loose

Gingivitis(2-3 mm pockets)

- gums become red

and bleed easily

Moderate

periodontitis(4-6 mm pockets)

- gum recession, bone

and tissue destruction

Periodontitis

Periodontitis is a severe gum infection

that can lead to tooth loss and other

serious health complications.

4

Untreated, can progress to

Increased prevalence of periodontitis in older age

FIGURE. Prevalence of total, mild, moderate, and severe periodontitis among adults aged ≥30 years, by age — National Health and Nutrition Examination Survey, United States, 2009–2010. This figure is a line graph that presents periodontitis in adults aged ≥30 years by level of severity (i.e., total mild, moderate, and severe). This figure demonstrates that the prevalence of mild and severe periodontitis remained relatively steady at <15% across all age groups.

Correlation between periodontitis and halitosis

Silva et al (2017) Journal of Clinical Periodontology

Link between periodontal disease and

non-communicable diseases

Nazir (2017) International Journal of Health Sciences

Gingivitis and Periodontitis – the importance of the oral biofilm

▪ The oral cavity is home to more

than 700 different bacterial

species

▪ Biofilms are formed by bacterial

communities which reside in

saliva-covered soft and hard

tissues

▪ Oral biofilms are associated

with infectious diseases such

as tooth decay (caries) and

periodontal disease

Gingivitis

Gingivitis can cause dusky red, swollen,

tender gums that bleed easily, especially

when you brush your teeth.

Healthy gums Severe periodontitis(more than 6 mm pockets)

- Extensive bone and

tissue loss, teeth can

become loose

Gingivitis(2-3 mm pockets)

- gums become red

and bleed easily

Moderate

periodontitis(4-6 mm pockets)

- gum recession, bone

and tissue destruction

Periodontitis

Periodontitis is a severe gum infection

that can lead to tooth loss and other

serious health complications.

8

Untreated, can progress to

Composition of biofilms

Periodontal disease Osteoimmunology

Silva et al (2015) J. Appl. Oral Sci.

receptor activator of nuclear factor-κB ligandreceptor activator of nuclear factor-κB osteoprotegerin

Probiotic Oral Therapy

Studies

11

Probiotic oral therapy studiesPre-clinical trials and important reviews in vitro and in animals

Evaluation – lactobacilli and/or bifidobacteria Authors / References

Oral adhesion and survival of probiotic and other lactobacilli and bifidobacteria in vitro Haukioja et al., Oral Microbiol Immunol. 2006

Do probiotics offer opportunities to manipulate the periodontal oral microbiota? Tueghels et al., J Clin Periodontol. 2011

Bifidobacteria inhibit the growth of Porphyromonas gingivalis but not of Streptococcus mutans

in an in vitro biofilm model

Jäsberg et al., Eur J Oral Sci. 2016

Clinical efficacy of probiotics as an adjunctive therapy to non-surgical periodontal treatment of

chronic periodontitis: a systematic review and meta-analysis.

Martin-Cabezas et al., J Clin Periodontol. 2016

Evaluation – Bifidobacterium lactis HN019™ Authors / References

Benefits of Bifidobacterium animalis subsp. lactis Probiotic in Experimental Periodontitis. Oliveira et al., J Periodontol. 2017

Effects of the probiotic Bifidobacterium animalis subsp. lactis on the non-surgical treatment of

periodontitis. A histomorphometric, microtomographic and immunohistochemical study in rats.

Ricoldi et al., PloS one 2017.

Effects of the probiotic Bifidobacterium animalis subsp. lactis on experimental periodontitis in

diabetic rats

Messora and Furlaneto, Conference

presentation at Vitafoods Europe, Geneva, 2017

12

Traditional treatment of periodontitis vs use of probiotics

New approach to improve treatment

outcomes: Probiotics

Teughels et al., (2011) J Clin Periodontol 38 (Suppl 11): 159-177

Invernici et al. (2018) J Clin Periodontol . 45(10):1198-1210.

Recent studies indicate that certain probiotics can have

positive effects in oral health including:

• Reduction in moderate and deep pockets

• Reduced probing depth

• Reduced bleeding upon probing

• Promotes a shift from periodontitis associated to healthy

oral microflora

• Decrease in pro-inflammatory markers

Traditional treatment for periodontal disease:

Scaling and Root Planing (SRP)

Planing

Scraping, smoothing of root surface

to allow gum tissue reattach better

to roots

Scaling

Cleaning that removes plaque

and tartar from gum line

13

https://www.ncbi.nlm.nih.gov/pubmed/30076613

Benefits of

B. lactis HN019™ in

experimental periodontitis

14

Benefits of B. lactis HN019™ in experimental periodontitis

Aim of the study

To evaluate microbiologic, histomorphometric, and

immunologic outcomes following topical administration of

B. lactis HN019™ in rats with ligature induced experimental

periodontitis in mandibular first molar (MFMs).

Study design

32 rats, divided to four groups of 8:

• control

• HN019™

• experimental periodontitis

• experimental periodontitis + HN019™

In probiotic groups each MFM were topically swabbed with 1

ml of 1.9 x 109 CFU B. lactis HN019™ on days 0, 3, and 7.

Oliveira et al., J Periodontol. 2017

15

Benefits of B. lactis HN019™ in experimental periodontitis

Experimental periodontitis + probiotic

▪ Group had more expression of

osteoprotegerin (OPG) and β-defensins vs.

experimental periodontitis –group

▪ Group showed decreased IL-1β and

receptor activator of nuclear factor-kappa B

ligand (RANKL) vs. experimental

periodontitis –group

Oliveira et al., J Periodontol. 2017

16

% DNA probe counts = percentage of the DNA count of each

species in relation to the total DNA count of the 40 bacterial species

evaluated. *Significant difference among groups (t test, P <0.05).

0

3

6

9

12

% D

NA

pro

be

co

un

ts

Group EP

Group EP + HN019™

Mean proportions of 40 species in the ligature biofilm

Effects of B. lactis HN019™ on non-surgical treatment of

periodontitis

Aim of the study

To evaluate the effect of B. lactis HN019™ together

with scaling and root planing (SRP) on ligature

induced experimental periodontitis.

Study design

32 rats, divided to four groups of 8:

• control,

• HN019™

• experimental periodontitis + SRP

• experimental periodontitis + SPR + HN019™

Probiotic groups received B. lactis HN019™ orally

in milk 109 CFU/10 ml for 15 days.


17

Effects of B. lactis HN019™ on the non-surgical treatment

of periodontitis

Experimental periodontitis + SPR + probiotic

▪ Group had reduced alveolar bone resorption

and attachment loss vs. experimental

periodontitis + SPR group.

▪ Group showed fewer osteoclasts, increased

expression of anti-inflammatory cytocines

and reduced expression of proinflammmatory

cytocines vs. experimental periodontitis +

SPR group.

* p<0.05

18


*

Ae

rob

ic/a

na

ero

bic

ba

cte

ria

ratio

Experimental groups

InterventionPlacebo

7.5

5.0

2.5

0.0

Effect of B. lactis HN019™ on ligature-associated microbiota.

B. lactis HN019™ gave greater bone volume,

reduced bone porosity and alveolar bone level

19


Table 1. Micro-CT analyses. Means and standard deviations (SD) of Bone Volume (BV), Bone Porosity (BP) and Alveolar Bone Level (ABL)

Human clinical trial

Effects of probiotic therapy in the

treatment of periodontitis: a study

of clinical, microbiological and

immunological profiles of the

host response

Invernici et al. (2018) J Clin Periodontol. 45(10):1198-1210.

AimTo evaluate the effects of the probiotic

therapy using Bifidobacterium lactis

HN019™ as an adjunct to non-surgical

periodontal treatment in patients diagnosed

with Generalized Chronic Periodontitis.

20

Effects of probiotic therapy in the treatment of periodontitis: a study of clinical, microbiological, and immunological profiles of the host response

Primary aim of the study

To evaluate the effects of the probiotic therapy using

Bifidobacterium lactis HN019™ as an adjunct to non surgical

periodontal treatment in patients diagnosed with Generalized

Chronic Periodontitis on clinical attachment loss (CAL).

Secondary aim of the study

To evaluate the following parameters before and after the treatment

of chronic periodontitis with oral administration of Bifidobacterium

lactis HN019™ associated with Scaling and Root Planing (SRP) or

SRP only.

• Probing pocking depth (PPD)

• Plaque index and bleeding on probing

• Microbial analysis of supra and subgingival plaque

• Quantification of IL-1ß, IL-8 and IL-10 in gingival crevicular fluid

21


Study design

Randomized, double-blind, placebo-controlled and parallel

clinical trial.

Inclusion criteria

• Age over 30 years

• 30% or more the sites with Clinical Attachment Loss (CAL)

and Probing Pocket Depth (PPD) ≥4 mm

• Presence of Bleeding on Probing (BOP)

• At least 5 teeth with one site with CAL and PPD ≥5mm

• Otherwise healthy

Subjects41 adults with generalized chronic periodontitis, one lozenge

twice a day in the morning and before bedtime for 30 days

• Placebo N=21: Lozenge

• HN019™ N=20: Lozenge with 1 x 109 Bifidobacterium lactis

HN019™

Follow up - 30 days and 90 days.

Human clinical trial - periodontal measurements and dental

treatments used

Dental Treatment: Scaling and Root Planing (SRP)

PI: Plaque Index - percentage of total number of

tooth parts with plaque against number of teeth

present.

BOP: Bleeding On Probing - bleeding that is

induced by gentle manipulation of the tissue at the

depth of tooth and gingiva interface.

y = GR: Gingival Recession

x = CAL: Clinical Attachment Loss - measured from

a fixed point - usually the cementoenamel junction - to

the base of the sulcus or periodontal pocket.

z = PD: Probing Depths - from gingival to the base of

the sulcus or periodontal pocket. The margin may

change with tissue swelling or recession.

22

Effects of probiotic therapy in the treatment of periodontitis: a study of clinical, microbiological, and immunological profiles of the host response

Primary aim of the study

To evaluate the effects of the probiotic therapy using

Bifidobacterium lactis HN019™ as an adjunct to non surgical

periodontal treatment in patients diagnosed with Generalized

Chronic Periodontitis on clinical attachment loss (CAL).

Secondary aim of the study

To evaluate the following parameters before and after the treatment

of chronic periodontitis with oral administration of Bifidobacterium

lactis HN019™ associated with Scaling and Root Planing (SRP) or

SRP only.

• Probing pocking depth (PPD)

• Plaque index and bleeding on probing

• Microbial analysis of supra and subgingival plaque

• Quantification of IL-1ß, IL-8 and IL-10 in gingival crevicular fluid

23


Study design

Randomized, double-blind, placebo-controlled and parallel

clinical trial.

Inclusion criteria

• Age over 30 years

• 30% or more the sites with Clinical Attachment Loss (CAL)

and Probing Pocket Depth (PPD) ≥4 mm

• Presence of Bleeding on Probing (BOP)

• At least 5 teeth with one site with CAL and PPD ≥5mm

• Otherwise healthy

Subjects41 adults with generalized chronic periodontitis, one lozenge

twice a day in the morning and before bedtime for 30 days

• Placebo N=21: Lozenge

• HN019™ N=20: Lozenge with 1 x 109 Bifidobacterium lactis

HN019™

Follow up - 30 days and 90 days.

Human clinical trial – study design

7 days

Inclusion

30 days

Intervention

60 days

Follow-up

Full mouth

supragingival

scaling

Proper home care

techniques

24


• Scaling and Root Planing (SRP) – Day 0

• Clinical Attachment Loss (CAL)

• Probing Pocking Depth (PPD)

• Gingival Recession (GR)

• Plaque Index (PI)

• Bleeding on Probing (BOP)

• Adverse Event (AE)

• Samples of Gingival Crevicular Fluid (GCF)

• Samples of plaque and saliva

• Clinical Attachment Loss (CAL)

• Probing Pocking Depth (PPD)

• Gingival Recession (GR)

• Plaque Index (PI)

• Bleeding on Probing (BOP)

• Adverse Event (AE)

• Samples of Gingival Crevicular Fluid (GCF)

• Samples of plaque and saliva

Number of copies/μL of B. lactis HN019™ genome

25


Test

Control

Only

probiotic group

had increased

numbers of

B. lactis HN019™

in subgingival

plaque samples at

30 days and 90

days.

HN

01

9™

ge

mo

me

co

pie

s/

l

Baseline

400000

300000

200000

100000

1000

800

600

400

200

0

(x102)

30 days 90 days

Aa

(9,064.9)

Aa

(13,828.8)

Ba

(13,353,018.9)

Ba

(23,477.6)

Ba

(2,884,499.1)

Ab

(137,009)

Positive changes in Clinical Attachment Loss (CAL)

at 60 days after intervention with HN019™

Bifidobacterium lactis HN019™ continues to improve Clinical Attachment Loss 60 days after the

intervention as an adjunct to non-surgical periodontal treatment in patients diagnosed with

Generalized Chronic Periodontitis

Probiotic B. lactis HN019™ Control p-value (delta)

Baseline (mm) 4.63 ± 0.42 4.70 ± 0.45 NS

30 days (change from baseline mm)

- 1.12 ± 0.44 - 1.01 ± 0.44 NS


- 1.15 ± 0.45 - 0.76 ± 0.41 0.008


Baseline (mm) 7.48 ± 0.53 7.62 ± 0.72 NS

30 days (change from

baseline mm) - 3.12 ± 1.27 - 2.54 ± 1.33 NS


baseline mm)- 3.45 ± 1.21 - 2.07 ± 0.97 0.0004

X: CAL

26


Moderate

pockets

Deep

pockets

Positive changes in Probing Pocking Depth (PPD)

at 60 days after intervention with HN019™

Bifidobacterium lactis HN019™ continues to improve Probing Pocket Depth 60 days after intervention

as an adjunct to non-surgical periodontal treatment in patients diagnosed with Generalized Chronic

Periodontitis

Moderate

pockets

Deep

pockets


Baseline (mm) 4.47 ± 0.20 4.44 ± 0.27 NS


- 1.18 ± 0.37 - 1.11 ± 0.41 NS


- 1.28 ± 0.41 - 0.94 ± 0.42 0.01


Baseline (mm) 7.27 ± 0.29 7.26 ± 0.35 NS


baseline mm) - 3.20 ± 1.00 - 2.79 ± 1.11 NS


baseline mm)- 3.52 ± 1.19 - 2.62 ± 0.88 0.01

Z: probing depth

27


Oral microbiota profiles of mean counts (×105) in gingival plaque

Probing depth 4-7 mm –

moderate pockets

▪ The bacterial profiles of mean counts

indicate significant differences between

the HN019™ test group and control

group after 30 and 90 days.

▪ After 90 days the HN019™ test group

indicates a significant increase in

Actinomyces and Streptococcus and a

significant decrease in Porphyromonas

gingivalis and Treponema denticola

compared to baseline.

▪ P. gingivalis and T. denticola are

associated with periodontal diseases.

HN019™ Control 90 days baseline

28


HN019™ induced positive changes in microbial complexes of

gingival plaque

Overall the test group

containing HN019™ indicates

significant changes in sub-

and supragingival plaque for

the following bacteria

compared to the control:

Red complex bacteria:

P. gingivalis and

T. denticola decreased

in probiotic group at 30

and still at 90 days(associated with periodontal

disease)

Blue complex bacteria:

Actinomyces and

Streptococcus

increased

29


Conclusions - positive effects of

Bifidobacterium lactis HN019™

Probiotic Bifidobacterium

lactis HN019™ has positive

effects in oral health

▪ Reduction in moderate and

deep pockets

▪ Reduced bleeding upon

probing

▪ Promotes a shift from

periodontitis associated to

healthy microbiota

30


Patients healing is

much improved after intervention

with Bifidobacterium

lactis HN019™.

This lowers the

cost of treatment

with less therapeutic

morbidity.

Low risk Moderate risk High risk

HN019™

100%

Control

30

5

65

52.5

4.7

42.8

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Patients at risk for periodontitis progression

Excellent stability

With the blending of different carriers, the probiotic

chewable tablets stability

Opportunity:

Probiotic chewable tablet supply well over minimum cell

count of 1.0E+09 CFU/tablet before shelf life.

1.00E+09

1.00E+10

1.00E+11

Ac

tivit

y B

ac

teri

a（

CF

U/g）

Test time

Stability of probiotics

Delivery formats

Probiotic tablet

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A presentation with bite. Improving oral health in an ...€¦ · Gingivitis and Periodontitis ... presentation at Vitafoods Europe, Geneva, 2017 12. Traditional treatment of periodontitis