PROBIOTICS, PREBIOTICS , SYNBIOTICS IN PERIODONTOLOGY

1. PROBIOTICS IN
PERIODONTAL
HEALTH AND DISEASE
PRESENTER : DR. SHRUTI PATIL
DEPARTMENT OF PERIODONTICS
Chatterjee A, Bhattacharya H, Kandwal A. Probiotics in periodontal health and disease. J
Indian Soc Periodontol.

2. INTRODUCTION
• Probiotics are live microorganisms
administered in adequate amounts
with beneficial health effects on the
host.
•Probiotics are nano soldiers which
refer to genera of organisms, playing
a crucial role in halting, altering, or
delaying periodontal diseases.

3. • It poses a great potential in arena of periodontics
in terms of plaque modification, halitosis
management, altering anerobic bacteria
colonization, improvement of pocket depth, and
clinical attachment loss.
• Probiotics are broadly categorised in two genus
Lactobaccilus and Bifidobacterium.

4. Lactobacillus species Bifidobacterium species Others
L. Acidophilus B. Bifidum S. Intermedius
L. Casei B. Breve Enterococcus faecalum
L. Crispatus B. Infantis Streptococcus salivarius
subsp,thermophilus
L. Fermentum B. Longum Yeast and moulds
L. Gasseri B. Lactis Bacilus cereus
L. Paracasei B. Adolenscentis Streptoccocus
thermaphilus
L. Plantarum
L. Reuteri
L. Rhamnosus
Weissella ceberia ,
Weissella cibaria
Steptococcus salivarius

5. PROPOSED MECHANISM OF
PROBIOTICS
Various mechanisms have been proposed for
probiotic actions.
Probiotics have been documented to
modulate host immunity both systemically
and locally.
Cutler CW, Jotwani R. Dendritic cells at the oral mucosal interface. J Dent Res.
2006;85:678–89.

6. • “Oral lymphoid foci” have been identified in
interdental papillae, which provides site for local
immune modulation.
• These were earlier thought to act on
gastrointestinal tract mucosa only.
Mechanism of action :
• Direct interaction.
• Competitive exclusion.
• Modulation of host immune response.
Grimaudo NJ, Nesbitt WE. Coaggregation of candida albicans with oral fusobacterium species. Oral Microbial Immunol.
1997;12:168–73

7. DIRECT INTERACTION :
• Probiotics interact directly with disease causing
microbes by production of antimicrobial
substances against periodonto pathogens .
• Antimicrobial substances produced :
Organic acids.
Hydrogen peroxide.
Bacteriocins.

8. PROBIOTICS ANTI MICROBIAL SUBSTANCES
Lactobacillus reutri Bacteriocins : reutrin and reutricyclin - high affinity
for host tissue and has anti- inflammatory effect by
inhibition of proinflamatory mediators.
Weissella ceberia . Catalase.
Weissella cibaria Hydrogen peroxide ( inhibits proliferation of
fusobacterium nucleatum )
Streptococcus salivarius Bacteriocins

9. COMPETITIVE EXCLUSION :
• Beneficial microbes directly compete with the disease
developing microbes for nutrition or enterocyte adhesion
site.
• Eg : lactobacillus casei shirota., lactobacillus rhamnosus
MODULATION OF HOST IMMUNE RESPONSE :
• Probiotics interact with and strengthen the immune
system.
• Decrease in pro inflammatory cytokines.eg. Lactobacillus
reuteri.
• Modulation of host defenses include the innate as well as
the acquired immune system.
Twetman S, Derawi B, Keller M, Ekstrand K, Yucel-Lindberg T, Stecksen-Blicks C, et al. Short term effect of chewing gum containing probiotics
lactobacillus reutri on levels of inflammatory mediators in GCF. Acta Odontol Scand

10. Probiotics stimulate antigen presenting cells OR dendritic
cells.
Modulate pathogen induced inflammation through “toll
like receptors” on dendritic cells.
Expression of TH1 and TH2.
TH1 response : Phagocytose intracellular pathogens.
TH2 response : Phagocytose extracellular pathogens .

11. OTHER PROPOSED MECHANISM
APOPTOSIS :
• Probiotics stimulate apoptosis of tumor cells
through end product formation.
• Inhibits apoptosis of mucosal cells.
• Protects mucosal epithelium barrier by
maintaining tight junction protein expression and
prevent apoptosis of mucous membrane .

12. PROBIOTICS
PRODUCTION OF
ANTIMICROBIAL
SUBSTANCES
COMPETITION OF
BINDING SITES
MODULATION OF
IMMUNITY
AGGREGATION
TO ORAL
BIOFILM
ADHESION
TO ORAL
MUCOSA
REINFORCING
ORAL
EPITHELIUM
MODULATION OF
INFLAMMATORY
RESPONSE
RESISTANCE TO PATHOGENIC
COLONISATION
PREVENTION OF
PERIODONTAL DISEASE
PREVENTION OF CARIES

13. Author
and year
Strain Mode Result
Xiaoli Hu
et.al. 2019
Lactobacillus casei
Shirota
probiotic drink Changed some bacteria related to caries.
overall microbiota structure remained
unaffected
Iniesta M
et.al. 2012
Lactobacillus reuteri Tablet Reduction in the number of selected
periodontal pathogens in the subgingival
microbiota, without an associated clinical
impact.
Penala
S,et.al.
2016
Lactobacillus salivarius
(2 × 109 CFU) plus
Lactobacillus reuteri
(2 × 109 CFU) per
capsule.
(SRP + probiotics)
subgingival delivery
of probiotics and
probiotic
mouthwash.
Offers clinical benefit in terms of pocket
depth reduction in moderate pockets and
reduced oral malodor parameters.
Twetman
S.et.al.
2009
Lactobacillus reuteri Chewing gum Reduction of pro-inflammatory cytokines
in GCF
Morales
A.et.al
2016
Lactobacillus
rhamnosus
Probiotic sachet as
an adjunct to non-
surgical therapy.
Oral administration of L. rhamnosus
resulted in similar clinical improvements
compared with SRP alone.
PERIODONTAL CLINICAL STUDIES DONE WITH PROBIOTICS

14. sweetened probiotic milk beverage fermented with the
bacteria strain Lactobacillus paracasei Shirota.

15. HALITOSIS MANAGEMENT
• Volatile sulphur compounds (VSC) are responsible
for halitosis.
Bacteria responsible for VSC production :
• Fusobacterium nucleatum.
• Porphyromonas gingivalis.
• Prevotella intermedia.
• Treponema denticola.
Shimazaki Y, Shirota T, Uchida K, Yonemoto K, Kiyohara Y, Iida M, et al. Intake of dairy product and
periodontal diseases: The hisayama study. J Periodontol. 2008;79:131–7

16. • A probiotic strain (Weissella cibaria) possesses
the ability to inhibit VSC production under both
in vitro and in vivo conditions.
• Co-aggregation of Fusobacterium nucleatum with
other periopathogens results in secondary
colonization of biofilm and contributes
substantially to VSC production in the oral cavity.
[Coaggregation, a mechanism by which genetically distinct bacteria
specifically recognize one another, may contribute to the retention
and enrichment of different species within these biofilms.]

17. • Hydrogen peroxide has been implicated in
maintenance of a stable ecological system, and
protecting against invading pathogens.
• Hydrogen peroxide is known to reduce
concentrations of sulphur gas significantly in vivo.
• Lactobacillus acidophilus and Lactobacillus casei
have been determined to inhibit the in vitro
proliferation of anerobic bacteria via the
production of a strong acid.

18. • Streptococcus salivaris produces bacteriocins,
which inhibit bacteria producing VSC.
• Recently, in a study it was shown that lozenges and
gum containing Streptococcus salivaris decrease
VSC in halitosis patients.
Kang MS, Kim BG, Chung J, Lee HC, Oh JS. Inhibitory effect of Weissella cibaria isolates on the production of volatile sulphur
compounds. J Clin Periodontol. 2006;33:226–32

20. FreshBreath Kit contains
BLIS K12™, a specific
strain of Streptococcus
salivarius.
Each FreshBreath Kit
contains (a 4 week
supply):
40 x FreshBreath
Lozenges containing BLIS
K12™ (peppermint
flavour)
1 x bottle of FreshBreath
Mouthwash – contains
Cetylpyridinium chloride
(CPC) is a cationic
quaternary ammonium
compound. Acts as
antiseptic.
1 x Tongue cleaner

22. Probiotics usage could be beneficial for the maintenance
of oral health, due to its ability to decrease the colony
forming units (CFU) counts of the oral pathogens.
• Current evidence is insufficient for recommending
probiotics for managing dental caries, but supportive
towards managing gingivitis or periodontitis.
• Future studies should only record bacterial numbers
alongside accepted disease markers or indicators.

23. • Most of the studies reviewed showed only a short term
benefit with regards to reduction in gingival
inflammation and probing depth reduction.
• Lasting clinical benefits were not seen in any of the
studies.
• Current regimens of probiotics in the treatment of
periodontal disease produce only short-term clinical and
microbiologic benefits.

24. NATURAL OPTIONS
• Nature has a huge source of pro- and pre-biotic
food.
Probiotics:
• fermented vegetables dishes made from turnips
and cabbage are quite popular in north Europe.

25. • Kombucha, a fermented tea thought to originate in Russia
or China, is another great source of beneficial bacteria
that is also dairy-free.
• Water kefir is a probiotic beverage similar to Kombucha
and Ginger Beer
Ritsema T, Smeekens SC. Engineering fructan metabolism in plants. J Plant Physiol. 2003;160:811–20

26. • Moroccan preserved lemons are naturally
fermented without the use of a starter.
•Coconut kefir is a probiotic beverage
prepared from young coconut water and a
starter culture.

27. • Sour pickles are the traditional alternative
to vinegar pickles and are prepared using a
simple solution of unrefined sea salt and
clean, chlorine-free water encouraging the
growth of lactobacillus, which customarily
outcompete pathogenic bacteria.

28. • Other sources include dairy products.
• Recently, hisayama study showed that daily
intake of dairy product containing lactic acid is
good for periodontal health.

29. Prebiotics:
• “A prebiotic is a selectively fermented ingredient
that allows specific changes, both in the
composition and/or activity in the gastrointestinal
microflora that confers benefits upon host well-
being and health.”
• They are termed as functional food not destroyed
while cooking.
Ritsema T, Smeekens SC. Engineering fructan metabolism in plants. J Plant Physiol.
2003;160:811–20

30. • Short-chain prebiotics, e.g., oligofructose act on
right side of the colon providing nourishment to
the bacteria in that area.
• Longer-chain probiotics, e.g., Inulin, are
predominantly in the left side of the colon.
• Full-spectrum prebiotics act throughout the
colon, e.g., oligofructose-enriched inulin (OEI).

31. • The majority of research done on prebiotics is
based on full-spectrum prebiotics, typically using
oligofructose-enriched inulin (OEI) as the
research substance.
Kleessen B, Hartmann L, Blaut M. Oligofructose and long-chain inulin: Influence on the gut microbial ecology of rats associated with a
human faecal flora. Br J Nutr. 2001;86:291–300.

32. Synbiotics:
• As probiotics are mainly active in the small
intestine and prebiotics are only effective in the
large intestine, the combination of the two may
give a synergistic effect.
• Appropriate combinations of prebiotics and
probiotics are synbiotics.
• Various preparations have been tried in
periodontal context with certain amount of clinical
success, these trials supports the use of probiotics
in field of periodontics.
Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of
prebiotics. J.Nutr. 125:1401–12.

34. • Co-administration of synbiotic along with
standard therapy is more efficacious than SRP
and doxycycline in the treatment of Aggressive
periodontitis.
• Synbiotics can be used in the routine
management of AP.

36. PREBIOTICS PROBIOTICS SYNBIOTICS
Non digestible special
form of fibre or
carbohydrates .
Iive active micro-
organism that when
administered in
adequate amount will
have beneficial effect
to its host .
Synbiotics are
combination of both
prebiotics and probiotics.
Powder form can survive
heat, cold, acid and time.
More fragile. Vunerable
to heat and stomach
acid.
Increases survival chances
of probiotics
Nourish the bacteria that
live in intestine.
Compete with bacteria
already present in gut.
Has synergestic effect.
Prebiotics are only
effective in the large
intestine.
Probiotics are mainly
active in the small
intestine .
Prebiotics act in large
intestine, probiotics act in
small intestine thus
synbiotics acts symbiosis.
Sources : onions,
soyabeans, bananas,
whole wheat food.
Yogurt, aged cheese,
kefir, kimchi.

37. SAFETY CONCERNS AND DOSAGE
• Probiotics organisms are classified by FDA
as generally regarded as safe (GRAS).
• The main observed adverse effects of
probiotics were sepsis, fungemia and GI
ischemia.
Mackay AD, Taylor MB, Kibbler CC, Hamilton-Miller JM. Lactobacillus endocarditis caused by a probiotic organism. Clin Microbiol
Infect. 1999;5:290–2

38. • Critically ill patients in intensive care units,
critically sick infants, postoperative and
hospitalized patients and patients with
immune-compromised complexity were the
most at-risk populations.
• Existing evidence suggests that probiotics are
safe, complete consideration of risk-benefit
ratio before prescribing is recommended.

39. • Studies on commercial preparations have reported
probiotics on label were not matching with the contents,
in commercial products misidentification of probiotics
bacteria is common.
• Lactobacillus acidophilus in many commercial
preparations either has no active species or had other
species.
• Another important concern is dose of probiotics
required for adequate action; various studies have
reported different values, 1×108-10, 1×109-10, 1×1010-
11

40. • Probiotic are supplied along with prebiotic in form
of powder sachet, gelatine capsules, or
suspension.
• “BION” commercially available in Indian market
(combination of pre- and pro-biotic) has 0.48
billon spores of Lactobacillus acidophilus,
Lactobacillus rhamnosus.

42. DESIGNER PROBIOTICS
• The term “Patho-Biotechnology” was introduced
by Sletor and Hill.
• It comprises of three basic approaches.
• Use of attenuated bacterial pathogens as vaccine.
• Isolation and purification of pathogen specific
immunogenic protein for direct application.
Sleator RD, Hill C. Patho-biotechnology; using bad bugs to make good bugs better. Sci Prog. 2007;90:1–14.

43. •Equipping probiotics bacteria with genetic
element necessary to overcome stress
outside host, inside host and antagonise
invading pathogens.
•Third approach is what is termed as
“designer probiotics”.

44. • Few studies done are limited to gut,
periodontal studies are lacking, but poses a
great potential in this field to develop.
• Designer probiotics have been employed in
treatment of HIV, also employs as a novel
vaccine delivery vehicle.

45. •Improving the stress tolerance profile of
probiotic cultures significantly improves
tolerance to processing stress and prolongs
survival during subsequent storage.
•This in turn contributes to a significantly
larger proportion of the administered
probiotics would reach the desired location
(e.g., the gastrointestinal
tract/periodontium) in a bioactive form.

46. REPLACEMENT THERAPY
•The term replacement therapy (also called
bacteriotherapy or bacterial interference) is
sometimes used interchangeably with
probiotics.
•But it differs from probiotics in following:
Wilson M. Manipulation of the indigenous microbiota. In: Wilson M, editor. Microbial inhabitants of humans. New York: Cambridge
University Press; 2005. pp. 395–416.

47. 1. Effector strain is not ingested and is applied
directly on the site of infection.
2. Colonization of the site by the effector strain is
essential.
3. Involves dramatic and long-term change in the
indigenous microbiota and is directed at
displacing or preventing colonization of a
pathogen.
4. Have a minimal immunological impact.

48. CONCLUSION
• Probiotics are counterparts of antibiotic thus are
free from concerns for developing resistance,
further they are body's own resident flora hence
are most easily adapted to host.
• A critical need to establish good periodontal
health for attaining good systemic health is of
utmost importance and probiotics are promising,
safe, natural, and side effects-free option, which
are required to be explored in depth for
periodontal application.

49. • Despite great promises, probiotics works
are limited to gut.
• Periodontal works are sparse and need
validation by large randomized trials.