Bugs that debugs: Probiotics.

The oral cavity harbors a diverse array of bacterial species. There are more than 600 species that colonize in the oral cavity. These include a lot of organisms that are not commonly known to reside in the gastrointestinal (GI) tract and also are more familiar: Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus rhamnosus, and Lactobacillus salivarius. The balance of all these microorganisms can easily be disturbed and a prevalence of pathogenic organisms can lead to various oral health problems including dental caries, periodontitis, and halitosis.

Probiotics are live microorganisms administered in adequate amounts with beneficial health effects on the host.[1] A few conventional foods containing probiotics are yogurt, fermented and unfermented milk, and soya beverages. The term “probiotics” was introduced in1965 by Lilly and Stillwell. Most often, they come from two groups of bacteria, Lactobacillus or Bifidobacterium. The most commonly used strains belong to the genera Lactobacillus and Bifidobacterium, which are commonly found in the oral cavity, including caries lesions.[2] These were the first probiotic species to be introduced into research (Lactobacillus acidophilus by Hull et al., 1984 and Bifidobacterium bifidum).[3] The mechanism involved is shown in Figure 1.

Figure 1

Theoretical possibilities for probiotics to affect periodontal health

Definition

World Health Organization (WHO) in 2001 defined probiotics as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.” Lilly and Stillwell were the first to use the term “probiotics.” Parker defined probiotics as organisms and substances which contribute to intestinal microbial balance. Fuller redefined probiotics as “a live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance.”

Antibiotics destroy the harmful bacteria that can cause infection, while also destroying the good bacteria that help to fight infection (WHO 2002).

Prebiotics are generally defined as not digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already established in colon, and thus in effect improve host health. These prebiotics include inulin, fructooligisaccharides, galactosoligosaccharides, and lactulose (WHO 2002).

Synbiotics are defined as mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract of the host.

The term replacement therapy (Bacteriotherapy) is sometimes used interchangeably with probiotics. Although both approaches use live bacteria for prevention or treatment of infectious disease, there are some slight differences (Victor 2010).[3] The concept is “bacterial Interference,” whereby one microorganism can prevent and/or delay the growth and colonization of another member of the same or a different ecosystem.

History

Metchnikoff, 1907: Ingesting yogurt with lactobacilli reduces toxic bacteria of the gut and prolongs life

Kipeloff, 1926: Stressed the importance of L. acidophilus for good health

Rettger, 1930s: Early clinical application of Lactobacillus

Parker, 1974: First to use the term probiotics

Fuller, 1989: Defined probiotics

Mechanism of Action

Vivek gupta et al.[4] in 2010 had given the following mechanisms:

Direct interaction

Probiotics interact directly with the disease-causing microbes, making it harder for them to cause the disease.[5]

Competitive exclusion

Beneficial microbes directly compete with the disease developing microbes for nutrition or enterocyte adhesion sites.[5]

Modulation of host immune response

Probiotics interact with and strengthen the immune system and help prevent disease.[5]

Uses

Elimination of lactose intolerance

Anti-diarrheal

Immunomodulatory

Antidiabetic

Anticarcinogenic

Hypocholesterolemic

Antihypertensive

Anticarcinogenic: Colon, breast, and others

Antiallergic

Anti-inflammatory diseases: Inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, pouchitis, and postoperative complications

Genetically modified probiotics

Oral vaccine development

Probiotics: Competitive Inhibition

They help to restore the balance of “good” bacteria and “bad” bacteria and facilitate the growth of healthy bacteria, i.e. Bifidobacterium and Lactobacillus. Bifidobacterium infantis inhibits the growth of Salmonella (O’Mahony, 2004).

Probiotics: Barrier Protection

Intestinal permeability to bacteria is increased with inflammation, i.e. Crohn's, ischemia (Nejdfors et al., 1998). Pretreatment with Lactobacillus plantarum 299v inhibits Escherichia coli intestinal permeability (Mangell et al., 2002). B. infantis prevents bacterial (Salmonella) translocation (O’Mahony, 2004).

Probiotics and Immune Function

Mononuclear cells incubated with lactobacilli produce higher levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1 (MacFarlane and Cummings, 1999). Bifidobacteria suppressed the proinflammatory mediators (TNF-α, IFN-γ, IL-12) in a murine model of IBD (IL-10 knockout) (McCarthy et al., 2003). In healthy volunteers, Lactobacillus rhamnosus increased phagocytic activity and natural killer (NK) tumor cell killing activity (Sheih et al, 2001).

Probiotics: Potential Uses

Infectious diarrhea in children (i.e. rotavirus)

Traveler's diarrhea

Antibiotic associated diarrhea

Clostridium difficile

Periodontal Diseases

Periodontal diseases are classified into two major types – gingivitis and periodontitis. Gingivitis is characterized by inflammation of gingiva, whereas periodontitis is a progressive, destructive disease that affects all supporting tissues of teeth, including the alveolar bone. The main pathogenic agents associated with periodontitis are P. gingivalis, Treponema denticola, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans (Socransky).[6] The treatment strategies conferred by probiotics against periodontal diseases are mainly thought to be either by inhibition of specific pathogens or by altering the host immune response through multifactorial causes.

Various probiotic organisms used in periodontal therapy are Lactobacillus, Bifidobacterium species, and Streptococcus species. These organisms can be delivered as food products (cheese, milk, yogurt) or supplements as chewing gum, lozenges, capsules, tablets, mouth rinses, sprays, etc.[4] Probiotics can be used in treatment of various periodontal conditions like, gingivitis, periodontitis, and halitosis.

Lactobacillus reuteri is known for its secretion of two bacteriocins, reuterin and reutericyclin, that inhibit the growth of a wide variety of pathogens. It has a strong capacity to adhere to host tissues, thereby competing with pathogenic bacteria. The anti-inflammatory effects on the intestinal mucosa lead to the inhibition of secretion of proinflammatory cytokines, or a direct or indirect beneficial effect of this bacterium on people with periodontal disease (Krasse). Consumption of probiotic milk drink containing Lactobacillus Casei reduced the MMP-3, elastase activity in students with plaque induced gingivitis.

Riccia and colleagues in 2007 studied the anti-inflammatory effects of Lactobacillus brevis in a group of patients with chronic periodontitis. It has the capacity to prevent the production of nitric oxide and, consequently, the release of prostaglandin E2 (PGE2) and the activation of MMPs induced by nitric oxide. During the fermentation process in milk, Lactobacillus helveticus produces short peptides that act on osteoblasts and increase their activity in bone formation. These bioactive peptides could thereby contribute in reducing the bone resorption associated with periodontitis.[7]

Chewing Gum “perio balance” is the first probiotic specifically formulated to fight periodontal disease. It contains a combination of two 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. Additional studies are required to evaluate the long-term effects of using these products.

Probiotics lower the pH so that plaque bacteria cannot form dental plaque and calculus that causes the periodontal disease. They produce antioxidants which prevent plaque formation by neutralizing the free electrons that are needed for the mineral formation. Probiotics are able to break down putrescence odors by fixating on the toxic gases (volatile sulfur compounds) and changing them to gases needed for metabolism. The most common probiotic strains belong to the genera Lactobacillus and Bifidobacterium. The species are L. acidophilus, Lactobacillus johnsonii, L. casei, L. rhamnosus, Lactobacillus gasseri, and L. reuteri.[8] Similarly, the Bifidobacterium strains include B. bifidum, Bifidobacterium longum, and B. infantis. Lactobacilli can produce different antimicrobial components including organic acids, hydrogen peroxide, low-molecular weight antimicrobial substances, bacteriocins, and adhesion inhibitors, and have gained prominence as probiotics. Streptococcus oralis and Streptococcus uberis have been shown to inhibit the growth of pathogens both in the laboratory and animal models.

Presence of S. oralis and S. uberis provides a good indication of health of periodontium. When these bacteria are absent from sites in the periodontal tissues, those sites are more prone to disease. The probiotic tablets (Wakamate D®), containing 6.7 × 108 colony forming units (CFU)/tablet of Lactobacillus salivarius WB21 and xylitol (280 mg/tablet), were originally prepared to contribute for the intestinal microbial balance by providing acid-tolerant L. salivarius WB21. Using these tablets, it was found that orally administered L. salivarius WB21 significantly decreased the plaque index and probing pocket depth of subjects who were smokers, suggesting clinical improvement of the periodontal condition by probiotic intervention. A significant reduction in salivary lactoferrin (Lf) levels was also observed for smokers at 8 weeks.

Probiotic species alter the balance of proinflammatory and anti-inflammatory cytokines secreted by epithelial cells. Elevated levels of TNF-α, IL-1, IL-6, and IL-8 are regarded as hallmarks of the inflammatory response in the intestine. The potentially protective role of probiotics in periodontal disease might benefit from adopting methods from studies in the gastrointestinal tract. However, so far, there have been no studies in this interesting area. Example for commercially available probiotic dietary supplement shown in the Figure 2.

Figure 2

Saccharomyces boulardii

L. reuteri and L. brevis are among the species able to affect gingivitis and plaque composition positively as well as being specific markers for periodontal disease. A significant decrease in gingival bleeding and a reduction in gingivitis were observed after a 2-week intake of probiotic species. This is due to the 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. L. salivarius WB21 reduces the prevalence of periodontal pathogens. This study stresses that a probiotic intervention could be a useful tool for the treatment of inflammation and the clinical symptoms of periodontitis (Mayanagi, 2009).[9] L. acidophilus present in a tablet named Acilact was first clinically tested by Pozharitskaia et al. in 1994 and they found improved clinical parameters in periodontitis patients and shifts in local microflora toward gram-positive cocci and lactobacilli.

Grudianov et al. in 2002 carried out a clinical study where they obtained a probiotic mix in the tablet forms, Acilact and Bifidumbacterin, and found normalization of microflora and reduction of signs of gingivitis and periodontitis. Shimazaki and colleagues used epidemiological data to assess the relationship between periodontal health and the consumption of dairy products such as cheese, milk, and yoghurt. The authors found that individuals, particularly nonsmokers, who regularly consumed yoghurt or beverages containing lactic acid, exhibited lower probing depths and less loss of clinical attachment than individuals who consumed few of these dairy products. By controlling the growth of the pathogens responsible for periodontitis, the lactic acid bacteria present in yoghurt would be in part responsible for the beneficial effects observed.

Breath malodor is a considerable social problem and majority of the pathologies (85%) causing halitosis are present in the oropharynx (tongue coating, gingivitis, periodontitis, tonsillitis). The common organisms implicated in halitosis are Fusobacterium nucleatum, P. gingivalis, P. intermedia, and T. denticola. These organisms degrade salivary and food proteins, and generate amino acids, which are in turn transformed into volatile sulfur compounds (VSCs). There will be recolonization of halitosis-causing bacteria after treatment is stopped. To prevent the regrowth of odor-causing organisms, pre-emptive colonization of the oral cavity with probiotics might have a potential application as adjuncts for both the treatment and prevention of halitosis.

Streptococcus salivarius was detected most frequently among people without halitosis and is therefore considered a commensal bacterium of the oral cavity. It produces bacteriocins which reduce the number of bacteria that produce VSCs. The use of gum or lozenges containing S. salivarius K12 reduced the levels of VSCs among patients diagnosed with halitosis. However, additional studies with larger patient cohorts are needed to confirm the long-term potential of probiotics in preventing and/or treating halitosis (Burton et al.).[10]

Products Available

Wakamate D

Perio balance–Chewing gum

Acilact

Align – A digestive care probiotic supplement

Cuturelle – A probiotic for digestive health

Ganeden Sustenex – A dietary probiotic used to boost the immune system and digestive health

Nature Made – A line of vitamins and supplements that has an acidophilus tablet

Other brands: Natrol, Nature's Bounty, Schiff, BioGaia, Sundown, Windmill, and more

Central Food Technology and Research Institute, Mysore

National Dairy Research Institute (NDRI), Karnal

Institute of Microbial Technology, Chandigarh

National Dairy Development Board, Anand

Nestle Pvt. Ltd., Panipat

Conclusion

Probiotics represent a new area of research in periodontal therapy. However, longitudinal studies are required to clarify the observed relationship between regular consumption of products containing probiotics and periodontal health. Realizing the immense potential of probiotics and their relevance in meeting the nutritional and health care requirements from the national perspective, NDRI, Karnal, took an initiative and formed a national core group on probiotics and its first meeting was held at NDRI, Karnal, on 5 March 2010 to discuss some pertinent issues related to probiotic status in India. The 2nd meeting of the core group was held at NASC complex, New Delhi, on 15 November 2010.