PROBIOTICS

Dr Nida Sumra

Introduction • Nobel Prize laureate Ilya Metchnikov in the early years of the 20th century -

Introduced concept of probiotic in his book on “prolongation of life”

• 1953 Kollath "Probiotics" was first introduced

Definition • Probiotics are defined as living microorganisms, principally bacteria, that are

safe for human consumption and, when ingested in sufficient quantities, have beneficial effects on human health, beyond basic nutrition.

• This definition has been approved by the United Nations Food and Agriculture Organization (FAO) and the World Health Organization (WHO).

• Probiotics are live microorganisms that when administered in adequate amounts confer health benefits upon the host.

• Japanese scientists - inactivated microorganisms or their cell components - beneficial effects on human health - these findings have broadened the concept of probiotics by abating the importance of live microorganisms

Foundation • Lactobacillus plantarum, L. rhamnosus and Lactobacillus lactis - effectively

reduce the levels of interleukin-8 before Helicobacter pylori infection of epithelial cells when the concentration of lactobacilli was 10ⁱ⁰ colony-forming units ⁄ ml.

• Probiotics to be combined with prebiotics, thus forming a symbiotic composition.

• Prebiotics - nondigestible carbohydrates used as a nutrient source by probiotic species in the gut that promote their establishment and extend their mode of action.

Species • Probiotic species - genera Lactobacillus and Bifidobacterium.

• The oral cavity has only recently been suggested as a relevant target for probiotic applications

• To be able to exert probiotic properties in the oral cavity – microorganism- resist the oral environment, defense mechanisms - adhere to saliva-coated surfaces, to colonize and grow in the mouth, and to inhibit oral pathogens.

Rationale • Taking into account the two major treatment strategies against periodontal

diseases, namely the elimination of specific pathogens and the suppression of a destructive host response, the probiotic approach may add value in achieving these treatment goals.

Is the oral cavity a natural habitat for probiotics?• Lactobacillus rhamnosus GG, one of the most frequently studied probiotic

microorganisms, has been found to be incapable of establishing permanent residence in the oral cavity.

• Probiotic products - regularly consumed, these species might become established for extended periods of time, and thus able to exert their healthrelated effects.

• Ko˜ll-Klais et al - The most prevalent lactobacilli species detected in healthy subjects were L. gasseri and L. Fermentum.

• The presence of L. gasseri was associated with less dental plaque and less gingival inflammation.

• It may be assumed that beneficial bacteria reside in the oral cavity and that the intricate interplay among species might provide favorable environmental conditions for periodontal health maintenance

Pathogenesis of periodontal disease and possibilities for probiotic therapy

• The bacterial biofilm that forms on all hard and soft oral tissues is considered to be the principal etiologic agent.

• The accumulation of bacteria within the biofilm, facilitated by poor oral health maintenance, predisposes to allogenic shifts in the microbial community, leading to the onset of periodontal inflammation .

• Probiotic therapy could be considered as a means of inhibiting oral biofilm development

• Recently, Aas et al - 700 species occupying specific ecological niches in the mouth.

• Predominantly gram-negative anaerobic microorganisms - initial destruction of the soft connective tissue and, subsequently, to the disruption of the underlying alveolar bone and ligament supporting the teeth.

• Tannerella forsythia, Porphyromonas gingivalis, Treponema denticola , A Actinomycetemcomitans.

Mechanism of action

• Stamatova I, et al 2008 - in vitro variation in the antimicrobial activity of Lactobacillus sp. - periodontal pathogens A. Actinomycetemcomitans and P. gingivalis .

• A. Actinomycetemcomitans strains- most susceptible species to lactobacilli under the conditions of this experiment.

Inhibition, by Lactobacillus bulgaricus, of the growth of Aggregatibacter actinomycetemcomitans (agar overlay method). The clear areas around the wells indicate zones of inhibition.

• Another approach demonstrating the ability of micro-organisms to integrate into established oral microbial communities is their co-aggregation capacity with F. nucleatum.

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• Chain microorganism in dental plaque formation, possessing the ability to co-aggregate with the majority of other bacteria in the oral cavity .

• Interspecies adhesion is mediated via protein ⁄ glycoprotein–carbohydrate cell-surface interactions.

Co-aggregation of bacilli-form Lactobacillus rhamnosus GG with the filamentous Fusobacterium nucleatum.

• Consequently, modifying the pathogenic potential of the microbiota within the oral biofilm would be an interesting strategy in combating periodontal disease .

• Aglar et al - Replacing pathogenic microorganisms with harmless bacteria.

• Recently Haukioja et al- probiotic lactobacilli (L. rhamnosus GG, Lactobacillus casei Shirota, L. casei ATCC 11578) may affect the oral ecology by specifically preventing the adherence of other bacteria and by modifying the protein composition of the salivary pellicle.

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• By two different methods, namely the binding to and the degradation of salivary proteins.

• Probiotic species have shown their ability to alter the balance of proinflammatory and anti-inflammatory cytokines secreted by epithelial cells. Elevated levels of tumornecrosis factor-a interleukin-1, interleukin-6 and interleukin-8 are regarded as hallmarks of the inflammatory response in the intestine.

• Probiotics also regulate immune responses by enhancing innate immunity and modulating pathogen-induced inflammation via toll-like receptor-regulated signaling pathways .

• Despite the fact that most probiotics belong to the genus lactobacilli or bifidobacteria, some authors have developed the idea that probiotic therapy is equivalent to replacement therapy, thus allowing any species capable of affecting pathogen adhesion to be considered a probiotic.

• Teughels et al. - repeated application of Streptococcus sanguinis, Streptococcus salivarius and Streptococcus mitis after root planing successfully reduced and maintained low levels of anaerobic species and black-pigmented bacteria.

• This study was the first to assess the role of commensal oral streptococci to modulate periodontal pocket recolonization..

Clinical evidence of probiotic effectiveness in periodontal disease

• Simauchi et al - A significant decrease in gingival bleeding and a reduction in gingivitis - after a two-week intake of probiotic species – effective colonization of the probiotic bacteria within the oral cavity.

• The oral administration of a tablet containing L. salivarius WB21 was able to decrease the plaque index significantly, and the pocket probing depth markedly, in subjects who were smokers.

• Prostaglandin E2 levels reduced and weaken matrix metalloproteinase activities in saliva

• People who have consumed yoghurt - L. rhamnosus on a daily basis host this microorganism in the saliva for up to 3 weeks after discontinuing yogHurt consumption.

• However, contradictory results were obtained by Yli-Knuuttila and colleagues who reported that a strain of L. rhamnosus colonized the oral cavity only temporarily and that consistent consumption of the probiotic would be necessary for long-term beneficial effects.

• Together, these results suggest that the probiotics used in consumer products could colonize the oral cavity.

• A particular concern- probiotic effects on periodontal disease relates to the means of administration of these bacteria. Generally, probiotics are delivered in dairy products (mainly fermented milks), as food supplements in tablet forms, or in soft drinks.

• However, these routes of administration cannot provide prolonged contact with oral tissues, facilitating probiotic adhesion to saliva-coated surfaces.

• A lozenge form or a chewing tablet or gum might better serve- frequency of intake needs further evaluation- inability of most probiotic species tested to reside permanently in the oral cavity.

• Sunstar (Etoy, Switzerland) recently began marketing the first probiotic specifically formulated to fight periodontal disease.

• Gum PerioBalance contains a patented combination of 2 strains of L. reuteri specially selected for their synergetic properties in fighting cariogenic bacteria and periodontopathogens.

• Each dose of lozenge contains at least 2 × 108 living cells of L. reuteri Prodentis.

• Users are advised to use a lozenge every day, either after a meal or in the evening after brushing their teeth, to allow the probiotics to spread throughout the oral cavity and attach to the various dental surfaces.

• Krasse and colleagues- beneficial effect of L. reuteri against gingivitis. After 14 days of ingesting the probiotic incorporated into chewing gum, the oral cavity of patients with a moderate to severe form of gingivitis had been colonized by L. reuteri and the plaque had been reduced.

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• Secretion of bacteriocins, reuterin and reutericyclin, that inhibit the growth of a wide variety of pathogens

• Strong capacity to adhere to host tissues, thereby competing with pathogenic bacteria

• Anti-inflammatory effects of L. reuteri on the intestinal mucosa, leading to inhibition of secretion of proinflammatory cytokines.

• Probiotic (L. casei 37) cell suspensions, when added to a collagenous periodontal dressing - considerable decrease in the number and frequency of isolation of aggressive microbial species from periodontal pockets, thus extending remission periods up to 10–12 months.

• Tablet forms of L. casei – Bifibumbacterin, Acilact, and Vitanar commercially available in Russia, have been marketed for oral administration to treat periodontal disease after routine mechanical debridement as follows: two tablets to be dissolved in the mouth, three times a day, for 20–30 days.

• In Russia, probiotics have been officially adopted as a preventive means for oral candidal infections and recommended to dental practitioners

• Shah et al – 2013 – doxycycline + probiotic – aggressive periodontits.

• Halitosis – decrease in VSC – shimazaki et al.

• Side effects – 0.05% - lactobacillus endocardidits – usually immunocompromised subjects.

• Marcotte et al. have studied a novel means to utilize the beneficial properties of probiotics.

• Although lactobacilli - could be effectively used in delivering antibodies against P. gingivalis.

• This type of approach, together with the innate immunomodulatory effects of probiotics, might offer interesting prospects in the future

Possible prebiotic applications from an oral health perspective

• Introduced by Gibson & Roberfroid in 1995, several decades after the probiotic model.

• By definition, prebiotics are selectively fermented ingredients that allow specific changes, both in the composition and ⁄ or in the activity of the gastrointestinal microflora that confer benefits upon host wellbeing and health

• Currently, only oligosaccharides in the fructo-oligosaccharide and galactooligosaccharide groups can be termed as prebiotics

• In order to be effective, a prebiotic must escape digestion in the upper gastrointestinal tract so that it can be released in the lower tract and used by beneficial microorganisms in the colon, mainly bifidobacteria and lactobacilli.

• Prebiotic effects depend on solubility, distribution, and branching and length of the chains of the molecules.

• Prebiotics cause their effects mostly through the metabolism of the bacteria they promote.

• Unlike probiotic bacteria, prebiotic carbohydrates do not undergo any changes during cooking, a characteristic that makes them interesting in the food industry.

• Trials have shown that feeding prebiotics can indeed change the composition of the intestinal microbiota towards more protective intestinal bacteria and subsequently alter systemic and mucosal immune responses of the host

• However, there are no studies exploring whether or not prebiotics have any function in enhancing probiotic activity in the oral cavity

• The prebiotic concept might still be adopted in the oral cavity if consuming prebiotic carbohydrates would indeed stimulate the putative probiotic strains to remain for longer in the mouth.

• However, in such cases the prerequisite remains the ability of the probiotic species to integrate itself into the oral environment, utilizing prebiotic nutritient sources that must not be hazardous for dental health.

Conclusion• Probiotics - counterparts of antibiotic - free from concerns for developing resistance,

further they are body’s own resident flora hence are most easily adapted to host.

• Probiotics- huge opportunity to treat diseases in a natural and non invasive way.

• Advances and accomplishments attained give us the ability to employ these friendly bacteria - nano soldiers in combating periodontal diseases.

• Despite great promises, probiotics works are limited to gut.

• Periodontal works are sparse and need validation by large randomized trials.

• It can be said probiotics are still in “infancy” in terms of periodontal health benefits, but surely have opened door for a new paradigm of treating disease on a nano – molecular mode.

References• Probiotics and periodontal disease. IVA STAMATOVA & JUKKA H. MEURMAN. Perio 2000 vol:51.

• Probiotics for Oral Health: Myth or Reality? Laetitia Bonifait, Fatiha Chandad, Daniel Grenier, PhDJCDA • www.cda-adc.ca/jcda • October 2009, Vol. 75, No. 8 •

• Probiotics: Health benefits in the mouth. IVA STAMATOVA, JUKKA H. MEURMAN. American Journal of Dentistry, Vol. 22, No. 6, December, 2009

• Probiotics in periodontal health and disease. Anirban Chatterjee, Hirak Bhattacharya, Abhishek Kandwal Journal of Indian Society of Periodontology - Vol 15, Issue 1, Jan-Mar 2011

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