Prebiotics, Probiotics and Synbiotics

8/10/2019 Prebiotics, Probiotics and Synbiotics

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PREBIOTICS, PROBIOTICS

AND SYNBIOTICSINPERIODONTALHEALTH


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INTRODUCTION

The term Probiotic' = "for life.(Greek)

First used in 1965, by Lilly and Stillwell

- for describing substances secreted by one organism

which stimulate the growth of another.

An expert panel commissioned by the Food and

Agriculture Organization (FAO) and the World Health

Organization (WHO) defined Probiotics as:

"live micro-organisms", which when administered in

adequate amounts confer a health benefit on the host.

The bacterial genera most commonly used in probiotic

preparations are Lactobacillus and Bifidobacterium .


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INTRODUCTION

Periodontics has entered the saga of major shifts in

treatment paradigm from nonspecific to specificapproach.

Now treatment options propose altering ecology of

niches, in order to modify pathological plaque to a

bioflim of commensalisms. Probiotics are live microorganisms administered in

adequate amounts with beneficial health effects on

the host.

Probiotics nano soldiers refer to genera oforganisms, which play a crucial role in halting,

altering, or delaying periodontal diseases.


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Traditionally, probiotics have been associated with gut

health.

Last decadean increasing number of established andproposed health effects of probiotic bacteria have been

reported,including :

enhancement of the adaptive immune response,

treatment or prevention of urogenital and respiratory tract

infections, and prevention or alleviation of allergies and

atopic disease in infants.

Recently, their beneficial effects on oral health have been

suggested.

A few reports have suggested the role of lactobacilli and

bifidobacteria in the prevention of oral infectious diseases

such as caries and periodontal disease


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Probiotics 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.


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DESIREDFEATURESOFAGOODPROBIOTIC

1. It should be a strain which is capable of exerting a

beneficial effect on the host animal.

2. It should be non pathogenic and non-toxic.

3. It should be capable of surviving and metabolising

in the gut environment, and should be able to

maintain genetic stability in oral microflora.

4. It should be present as viable cells, preferably in

large numbers.

5. It should be stable and capable of remaining

viable for periods under storage and field

conditions.


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PROPOSEDMECHANICSOFPROBOTICS:

Various mechanisms have been proposed for

probiotic actions.

Probiotics have been documented to modulate

host immunity both systemically and locally.

Recently, 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


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1. Probiotics stimulate dendritic cells (antigen

presenting cells) resulting in expression of Th1 (T-

helper cell 1) or Th2 (T-helper cell 2) response,which modulates immunity.

Probiotics enhances innate immunity and modulate

pathogen induced inflammation through Toll-like

receptors on dendritic cell. Intracellular pathogensare phagocytosed by Th1 response, while

extracellular pathogens are taken care by Th2

response.

Probiotics can mimic response similar to apathogen but without periodontal destruction


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2. Other proposed mechanisms include Glycoprotein

carbohydrate cell surface interaction mediated

by inter species interactions.

Lactobacillus casei, Lactobacillus bulgaricus,

Lactobacillus rhamnosus, Lactobacillus acidophilus

co-aggregate with Fusobacterium nucleatum.

Lactobacillus rhamnosus, and Lactobacillus

paracaseihave strong binding activity to primary

pellicle. Lactobacillus rhamnosus, Lactobacillus

casei shirota, Lactobacillus caseiATCC 11578

prevent adherence of bacteria to salivary pellicle byaltering its composition.


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3. Aggregation alteration is another important

proposed mechanics as Hetrofermentative

Lactobacillusis the strongest inhibitor ofAggregatibacter actinomycetem comitans,

Porphyromonas gingivalisand Prevotella

intermedia.

Fusobacterium nucleatumaggregate withWeissella ciberiain preference to Treponema

denticolaand Porphyromonas gingivalis.

Lactobacillus rhamnosusco-aggregates with

Fusobacterium nucleatum.


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4. Apoptosis is another proposed mechanism.Probiotics stimulate apoptosis of tumor cells

through end product formation. Probiotic mixture has also been reported to protect

epithelium barrier by maintaining tight junctionprotein expression and prevent apoptosis ofmucous membrane.

The oral anerobic bacteria exhibit a higher degreeof susceptibility to hydrogen peroxide than do othergenera of aerobic or facultative anerobic bacteria.

Weissella cibariaisolates generated a substantial

quantity of hydrogen peroxide, which was sufficientto inhibit the proliferation of Fusobacteriumnucleatum.


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5. Decrease in pro inflammatory cytokines by

probiotics ingestion is another mode of action as

seen in the GCF of patients on chewing gumcontaining Lactobacillus reutri.

Lactobacillus salivarisand Lactobacillus gasseri

show strong inhibition of periopathogenic bacteria.

Secretion of bacteriocins by Lactobacillus reutri,e.g., reutrin and reutricyclin inhibits growth of

pathogens and has high affinity for host tissue and

has anti- inflammatory effect by inhibition of

proinflamatory mediators.


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In a one-way crossover, open-label placebo-

controlled study Kang et al.included 72 volunteers.Subjects rinsed in morning twice with 15 ml rinse

containing probiotics strain. Rinsing was repeated

in the afternoon and in the evening, after brushing.

There was a significant, 20% reduction in plaque

scores when the Weissella cibariaCMS1-

containing rinse was used. These results indicate

that the Weissella cibariaisolates possess the

ability to inhibit biofilm formation.


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Another parallel open label placebo controlled study

by Hillman et al. on 24 gnotobiotic rats, including

single baseline application resulted significantdecrease levels ofAggregatebacter actinomycetum

comitans when compared with placebo groups.

Another study by Grudianov et al. using mixture of

probiotics also reported improvement of clinical signof gingivitis. Probiotics have also been employed as

antimutagenic and anticarigenic agents.


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The initial studies of the use of probiotics for enhancing

oral health were for the treatment of periodontal

inflammation. Lactobacillus reuteribrought about a significant reduction

in gingivitis in a study done by Krasse et al.

o The oral administration of tablet containing L. salivarius

WB21 was found to be able to decrease the periodontalindex and pocket probing depth (PD) in smokers

specifically.

Recently, an in vitrostudy done by Nara et al. on

Lactobacillus helveticusdemonstrated release of

short peptide stimulate osteoblast to promote bone

formation, thus proposing important role in repair of

periodontal bone destruction


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Increase in remission period upto 1012 weeks was

reported in periodontal dressing containing

Lactobacillus caseiwas reported by Volozhin.A parallel open label study by Ishikawa enrolled 84

subjects; consuming tablets containing

Lactobacillus salivaris T1 2711strain 5 times a day

for 8 weeks resulted in decrease in blackpigmented anerobic rods.

A similar study by Matsuka reported decrease

bleeding on probing and decrease in

Porphyromonas gingivaliscount.


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A study done on release of pro inflammatory

cytokine on Lactobacillus brevisby Ricca et al. and

Lactobacillus reutriby Svante Twetman et al.

showed decreased levels, improving the clinicalsigns of gingivitis.

Teughels et al. conducted a split mouth design

study on 32 beagle dogs with artificially created

pockets, bacterial pellets Streptococcus sanguisKTH-4, Streptococcus salivarius TOVE, and

Streptococcus mitis BMSwere applied locally in

designated periodontal pockets at baseline, 1, 2,

and 4 weeks, result showed decrease in anerobicbacteria and Campylobacter rectuswith decrease

pocket recolonization and bleeding on probing

when compared with controls.

P O O CS G S


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PROBIOTICSINGENERALUSE

Proven indication

1. Diarrhoea

2. Reduction of antibiotic associated side effect

Possible indication

1. Dental caries and periodontal health

2. Food allergies and lactose intolerance

3. Atopic eczema4. Prevention of vaginitis

5. Urogenital infections

6. Irritable bowel disease

7. Cystic fibrosis

8. Traveller's diarrhoea

9. Enhance oral vaccine administration

10. Helicobacter pyloriinfection

11. Various cancers


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OBSERVEDEFFECTSONHALITOSIS

Volatile sulphur compounds (VSC) are responsible

for halitosis. A probiotic strain (Weissella cibaria)possesses the ability to

inhibit VSC production under both in vitroand in

vivoconditions. It possesses great potential as

novel probiotic for use in the periodontium. Co-aggregation of Fusobacterium nucleatumwith other

periopathogens results in secondary colonization of

biofilm and contributes substantially to VSC

production in the oral cavity


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Lactobacillus acidophilusand Lactobacillus casei

have been determined to inhibit the in vitro

proliferation of anerobic bacteria via the production ofa strong acid.

Streptococcus salivarisproduces bacteriocins, which

inhibit bacteria producing VSC.

Recently, in a study it was shown that lozenges andgum containing Streptococcus salivarisdecrease VSC

in halitosis patients.


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Bacteriophages, viruses that kill bacteria, have

been detected in oral pathogens, such as

Actinobacillus actinomycetemcomitans, and they

may playa role in the pathogenicity. Recently, it hasbeen showed experimentally that phages against

Enterococcus faecal led to reduction of bacterial

vitality in root canals infected with this organism.


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To exert their action in the oral cavity, the probiotic

microorganism should :

be able to resist the oral environmental conditions anddefense mechanisms,

be able to adhere to saliva-coated surface,

colonize and grow in the mouth and to inhibit oral

pathogens. So there is a need to develop the probiotic strain and

species that can resist oral environmental conditions and

can bring their antimicrobial action.


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Prebiotics by definition are the non-digestible food

ingredient that confers benefits on the host by selectivelystimulating the growth and/activity of one bacterium or a

group of bacteria in the colon, and thus improve the host

health.

Oligosaccharides in the group of fructo-oligosaccharidesand galactosaccharides are the commonly studied

prebiotics.

They escape digestion in the upper gastrointestinal tract

so that they can be released in the lower tract and usedby beneficial microorganisms in the colon, mainly

bifidobacteria and lactobacilli.

PREBIOTICS


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Prebiotics serve as a food source for probiotics.

The probiotics feed off the prebiotics and increase in number.

Different probiotics have different actions in the gut. Each

probiotic species provides a distinctive health benefit.

Therefore, an increase in the number of probiotics positivelyimpacts the digestive system by improving digestive health

such as reducing the symptoms of irritable bowel syndrome

and inflammatory bowel diseases (e.g. Crohnsdisease);

promoting regularity; reducing the growth of harmful

bacteria; synthesizing vitamins (primarily B vitamins);

decreasing lactose intolerance; improving serum cholesterol

levels; and decreasing the risk of certain cancers.

RELATION BETWEEN PREBIOTICS AND PROBIOTICS


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Synbiotics are products that contain both probiotics and

prebiotics.These products have the goodbacteria (probiotics) and

the non-digestible carbohydrate source (prebiotics) to

encourage the growth of beneficial bacteria.

Fermented dairy products (yogurt and kefir) aresynbiotic because they contain live bacteria and the food

source needed for them


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The synbiotic concept was first introduced, along with

prebiotics, as:

mixtures of probiotics andprebiotics that beneficiallyaffect the host by improving the survival and

implantation of live microbial dietary supplements in the

gastrointestinal tract, by selectively stimulating the

growth and/or by activating the metabolism of one or alimited number of health-promoting bacteria, thus

improving host welfare (Gibson & Roberfroid 1995).

Since, there have been many in vitro and in vivo studies

focusing on the application of prebiotics, firstly in health

and gradually in disease states.

Only recently have studies on synbiotics started to

emerge with the main focus being on applications against

disease.


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Probiotics improve health in different ways . Thehealth benefits conferred by probiotic bacteria arestrain specific . Some strains increase phagocytic

activity of peripheral blood leukocytes, othersstrains promote production of mucosal antibodiesreducing the trans-mucosal transfer of antigens.This strengthens the mucosal barrier function .Other probiotic strains increase cytokine production

such as interleukin 6 (IL-6) .. C- reactive protein hasa relatively short half-life making it useful inmonitoring infection, inflammation and response totreatment . IL-6 is a pro-inflammatory cytokinewhich stimulates the production of acute phase

proteins (such as CRP) . It is readily detected inserum during inflammation and indicates thepresence of infection.


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MECHANISMOFACTIONOFPROBIOTICS

1. Probiotics improve colonization resistance to gut

pathogens by reinforcing the mucosal barr ier andrestoring normal gut micro ecology after diarrhea.

If the intestinal micro flora is deficient, antigen

transport is increased.

Probiotics have been shown to normalize an increasedpermeability. Binding is considered to be the first step

in pathogenesis, and binding of bacteria to the intestinal

mucosa or mucus may allow the colonization.

Probiotics compete with pathogens for binding sites

and available substrates.

Probiotics also seem to diminish the rate of

progression from inflammation through dysplasia to

colon cancer in experimental animals.


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2. Lactobaci l lus acidoph i lus, Lactobaci l lus

reuter i , Lactobaci l lus casei GG, or

Bi f idob acter ium animal isin the GI-tract of mice

prolonged their survival and decreased the severity

of mucosal and systemic candidiasis by modulating

immune responses,decreasing the number of C.

albicans in the alimentary tract, and by reducing thenumbers of orogastric infections.The results

demonstrated not only that probiotics bacteria have

biotherapeutic potential for prophylaxis against and

therapy of this fungal disease, but also thatprobiotic bacteria protect mice from candidiasis by

a variety of immunological (thymic and extrathymic)

and non immunological mechanisms.


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3.Probiotics can also activate and modulate the

immune system, and they have been shown toreinforce gut defence by immune exclusion, immune

elimination, and immune regulation.

The intestinal micro flora is associated with the

development of the immune system in the gut duringinfancy and early childhood


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PROBIOTICS, ORAL BIOFILM AND MICROFLORA

Direct interactions may include

Involvement in binding of oral microorganisms toproteins (biofilm formation).

Action on plaque formation and on its complex

ecosystem by compromising and intervening

with bacteria to bacteria attachments. Involvement in metabolism of substrate (competing

with oral microorganisms of substrates available)

Production of chemicals that inhibit oral bacteria

(antimicrobial substances).


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Indirect interactions may include:

modulating systemic immune function effect onlocal immunity, effect on non- immunologic defencemechanisms, regulation of mucosal permeability,selection pressure on developing oral microfloratowards colonization by less pathogenic species.

Effect of probiotics on the induction and

maintenance of oral tolerance has been recentlystudied through lactobacillus paracasei (NCC2461), lactobacillus johnsonii (NCC 533) andBifidobacterium lactis Bb12 (NCC 362) on to bovinebeta-Iacto globulin (BlG) that was investigated in

mice. This study had provided evidence thatprobiotics modulate the oral tolerance to BlG ingnotobiotic mice.

D


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DESIGNERPROBIOTICS

Probiotics bacteria equipped with genetic elementnecessary to overcome stress outside host, inside hostand antagonise invading pathogens.

probiotics are engineered to express receptor mimicstructures on their surface.

Designer probiotics have been employed in treatment of

HIV, also employs as a novel vaccine delivery vehicle. Improving the stress tolerance profile of probiotic

cultures significantly improves tolerance to processingstress and prolongs survival during subsequent storage.This in turn contributes to a significantly largerproportion of the administered probiotics would reachthe desired location (e.g., the gastrointestinaltract/periodontium) in a bioactive form.


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REPLACEMENTTHERAPY

The term replacement therapy (also called

bacteriotherapy or bacterial interference) issometimes used interchangeably with probiotics.

But it differs from probiotics in following:

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 displacingor preventing colonization of a pathogen.

4. Have a minimal immunological impact


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Teughels et al. employed this term as probiotics

and conducted studies, with application of

Streptococcus salivaris, Streptococcus mitis,Streptococcus sanguis, repeatedly on root surfaces

after scaling and root planning have resulted

decrease number of periopathogens.

It refers to the basic idea of replacing pathogenicbacteria by supplying commensalisms, which have

same affinity for tooth surface adherence.


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Some cases of bacteraemia and fungenaemia have

been reported in immunocompromised individualsin gut syndrome and chronic diseases.

Lactobacillus endocarditis have been reported after

dental treatment in a patient taking Lactobacillus

rhamnosus. Reported cases of infection are extremely rare

accounting to 0.050.4% of infective endocarditis

and bacteraemia.

Liver abscess was reported in an individual onLactobacillus rhamnosusGG.

SAFETY CONCERNS

CONCLUSION


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CONCLUSION

Probiotics are counterparts of antibiotic thus are free

from concerns for developing resistance, further theyare body's own resident flora hence are most easilyadapted to host.

With fast evolving technology and integration ofbiophysics with molecular biology, designer probioticsposes huge opportunity to treat diseases in a natural

and non invasive way.A critical need to establish good periodontal health for

attaining good systemic health is of utmost importanceand probiotics are promising, safe, natural, and sideeffects-free option, which are required to be explored indepth for periodontal application.

Advances and accomplishments attained give us theability to employ these friendly bacteria (probiotics) asnano soldiers in combating periodontal diseases


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T

H

A

N

K

Y

O

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Criteria of an ideal microorganism used asprobiotics:

1. High cell viability, resistant to low ph and acids

2. Ability to persist

3. Adhesion to cancel the flushing effect4. Able to interact or to send signals to immune cells

5. Should be of human origin

6. Should be non pathogenic

7. Resistance to processing

8. Must have capacity to influence local metabolicactivity

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Prebiotics, Probiotics and Synbiotics

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