|Year : 2013 | Volume
| Issue : 3 | Page : 114-119
Probiotics and periodontal diseases: The link
Nymphea Pandit1, Inder kumar Pandit2, Deepika Bali1, Saloni Oberoi1
1 Department of Periodontics, Dental College and Hospital, DAV © Centenary Dental College and Hospital, Yamuna Nagar, Haryana, India
2 Department of Pedodontics, Dental College and Hospital, DAV © Centenary Dental College and Hospital, Yamuna Nagar, Haryana, India
|Date of Submission||15-Feb-2013|
|Date of Acceptance||14-May-2013|
|Date of Web Publication||12-Dec-2013|
Department of Periodontics, D.A.V. Centenary Dental College and Hospital, Yamuna Nagar, Haryana
Source of Support: None, Conflict of Interest: None
The interest in probiotics and the modulation of the microbiota for restoring and maintaining health have gained a lot of attention over the past decade. Probiotics have been extensively studied for their health promoting effects. However, in the past few years probiotics have also been investigated in the oral health perspective. In the field of periodontics, probiotics have come up as an attractive alternative to antibiotics. They target particular periodontal pathogens, thus increasing the long-term success of periodontal therapy. This review evidence the use of various probiotic strains in periodontal diseases.
Keywords: Bifidobacterium, Lactobacillus, periodontal diseases, probiotics
|How to cite this article:|
Pandit N, Pandit Ik, Bali D, Oberoi S. Probiotics and periodontal diseases: The link
. Indian J Oral Sci 2013;4:114-9
| Introduction|| |
Microbial cultures have been used for thousands of years in food and alcoholic fermentations and in the past century have been investigated for their ability to prevent and cure a variety of diseases. This led to the coining of the term probiotics or "pro-life."  Endorsed by the Food and Agriculture Organization and the World Health Organization, the definition of probiotics, in 2001, describes them as live micro-organisms, which when administered in adequate amounts confer health benefits on the host. Most of the species ascribed as having probiotic properties belong to the genera Lactobacillus and Bifidobacterium and these bacteria are generally regarded as safe. 
In gastro-intestinal applications, it has been recommended for probiotics to be combined with prebiotics; thus, forming a symbiotic composition with proven health benefits. Prebiotics are non-digestible food ingredients such as fructooligosaccharides, lactulose and inulin that beneficially affect the host by selectively stimulating growth and/or increase activity of a limited number of probiotic like bacteria in a colon. The most commonly used prebiotics are carbohydrate substrates (e.g., dietary fiber) with the ability to promote the components of the normal intestinal micro flora, which may evince a health benefit to the host. 
Probiotics can improve patient condition in medical disorders such as diarrhea, gastroenteritis, short-bowel syndrome and inflammatory intestinal diseases (Crohn's disease and ulcerative colitis), cancer, immunodepressive states, inadequate lactase digestion, pediatric allergies, growth retardation, hyperlipidemia, liver diseases, infections with Helicobacter pylori, genitourinary tract infections and others.  Considering the particular activities of probiotics and their inhibitory effect on the growth of pathogens, research interest has been extended to the oral cavity where probiotics may also exert their therapeutic or preventive effect on the development and progression of common oral diseases. 
The clinical manifestation of periodontal disease result from a complex interplay between the etiologic agents, specific bacteria found in the dental plaque and the host tissues. The oral bacteria lives in harmony with its host, but under specific conditions (increased mass and/or pathogenicity, suppression of beneficial bacteria and/or reduced host response), disease can occur. Periodontal diseases can be managed by either inhibition of specific pathogens or affecting the host response. New strategies for periodontal disease management have been emerging as more is learned about the role of the host response. Since the primary etiological factors for the development of periodontal disease are bacteria in supra- and sub-gingival biofilm, efforts for disease prevention and treatment are mainly focused on pathogen reduction and strengthening of the epithelial barrier; thus, contributing to decreased susceptibility to infection. With the emergence of multi-resistant strains, antibiotic resistance has developed and has leads to seek other means of combating infectious diseases. Probiotic bacteria, may favor periodontal health if able to establish them in oral biofilm and inhibit pathogen growth and metabolism. So, periodontitis could benefit from orally administered probiotics. The presence of periodontal pathogen could be regulated by means of antagonistic interactions. 
With increasing understanding that beneficial microbes are required for health, probiotics may become a common therapeutic tool used by health-care practitioners in the not-too-distant future.
| History|| |
The scientific foundation of probiotics was laid down by Ukrainian Bacteriologist, Eli Metchnikoff in 1907 at Pasture Institute of Paris. In his book "Prolongation of life," he developed a theory that senility in humans is caused by poisoning of the body by the products of some of these bacteria (intestinal auto-intoxication). This Nobel Laureate proposed that consumption of fermented milk would seed the intestine with harmless lactic-acid bacteria and decrease the intestinal pH and that this would suppress the growth of proteolytic bacteria. 
Bifidobacterium was first to be isolated and administration of bifidobacteria was recommended to infants suffering from diarrhea. A strain of Escherichia More Details coli (E. coli Nissle) was isolated which is one of the few examples of non lactobacillus probiotics. ,
In 1950, a probiotic product was used as a drug for the treatment of scour among pigs. Lilly and Stillwell (1965)  introduced the term probiotics. Mann and Spoering in 1974 discovered that the fermented yogurt reduced blood serum cholesterol. In 1984, Hull identified the first probiotic species, the lactobacillus acidophilus. Later in 1991, Holcombh identified bifidobacterium bifidum. World Health Organization in 1994 described the probiotics as next most important approach in immune defense system following antibiotic resistance. Patients having Clostridium difficile infections with Saccharomyces boulardii and found this to be effective in shortening the duration of infection. Several probiotics have been shown to shorten the duration of acute watery diarrhea caused by rotavirus in children. ,,
In 1954 Kragen  reported, a beneficial effect of lactic acid bacteria on inflammatory infections of the oral mucosa. The presence of periodontal pathogens could be regulated by means of antagonistic interactions. Decrease in gingival bleeding and reduced gingivitis has been observed by Krasse et al.  with the application of Lactobacillus reuteri. Russian reports have shown the use of probiotics in the treatment of periodontitis (Kõll-Klais et al. 2005, Grudianov et al. 2002, Volozhin et al. 2004) ,, Periodontal inflammation has been reduced by the administration of two probiotic tablet forms Bifidumbacterina and Acilact (Grudianov et al. 2002). Studies by Volozhin et al. 2004 have also shown that a periodontal dressing containing Lactobacillus casei, strain 37 can reduce the number of most common periodontal pathogens and extend remission up to 10-12 months. Patients with different periodontal diseases such as gingivitis, periodontitis and pregnancy gingivitis, were locally treated with a culture supernatant of a L. acidophilus strain. Significant recovery was reported for almost every patient. Kõll-Klais et al. (2005)  reported that resident lactobacilli flora inhibits the growth of Porphyromonas gingivalis and Prevotella intermedia to 82% and 65%, respectively. Teughels et al. in 2007  introduced a novel concept suggesting that recolonization of a gingival pocket after scaling and root planning might be tailored by introducing microbes capable of inhibiting adhesion of common periodontal pathogens.
| Criteria of an Ideal Micro-organism Used as Probiotics|| |
Overall, probiotics are simply micro-organisms that impart health benefits to the host. They are generally bacteria, such as Lactobacillus and bifidobacteria strains. In order to be able to exert its beneficial effects; a successful potential probiotic strain is expected to have a number of desirable properties.
- Non-toxic and non-pathogenic preparation
- Produce beneficial effect
- Should withstand gastrointestinal juice
- Should have good shelf life
- Should replace and reinstate the intestinal microflora.
| Composition of Probiotic|| |
The list of such micro-organisms continue to grow and includes strains of lactic acid bacilli (e.g., Lactobacillus and Bifidobacterium), a non-pathogenic strain of E. coli (e.g. E. coli Nissle), Clostridium butyricum, Streptococcus salivarius and S. boulardii (a non-pathogenic strain of yeast). Different types of probiotics are shown in [Figure 1]. Strains of bacteria that have been genetically engineered to secrete immunomodulators (such as interleukin-10 [IL-10] or trefoil factors) and these have the potential to favorably influence the immune system. 
A probiotic may be made out of a single bacterial strain or it may be a consortium as well (may contain any number up to eight strains). The advantage of multiple strain preparations is that they are active against a wide range of conditions and in a wider range of animal species. 
The various means of administration of probiotics for oral health purpose that have been studied are: 
- Mouth rinse
- Capsule, liquid
Chewing gum "perio balance" is the first probiotic specifically formulated to fight periodontal disease. It contains two strains of L. reuteri specially selected for their synergistic properties in fighting cariogenic bacteria and periodontopathogens. Each dose of lozenge contains at least 2 × 10 8 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. PerioBiotic™ (Designs for Health, Inc.,) tooth paste is an all-natural, fluoride-free oral hygiene supplement containing Dental-Lac™, a functional Lactobacillus paracasei probiotic not found in any other toothpaste. Additional studies are however required to evaluate the long-term effects of using these products. 
The following probiotic drugs are available in the Indian market:
- ViBact capsules/sachets (USV),
- Binifit capsules/sachets (Ranbaxy),
- Becelac PB capsules (Dr. Reddy's Labs),
- Vizyl capsules/sachets (Unichem),
- Econova capsules (Glenmark),
- Biors sachets (Tablets India Ltd.) and
- Gutpro capsules/sachets (JBCPL),
- Ecoflora capsules (Tablets India Ltd.).
| Probiotics and Periodontal Diseases|| |
Gingivitis and periodontitis are the most common diseases with microbial etiology affecting the periodontium. Periodontitis is characterized by a progressive destruction of the supporting structures of the teeth. It is the result of inflammatory responses to dental plaque in a susceptible host. Bacteria may also directly cause tissue damage due to virulence factors, such as toxins and enzymes. The inflammatory response including an increased flow of gingival crevicular fluid (GCF) and a rise in pH favors the Gram-negative, proteolytic species thus leading to an ecological shift as suggested by the ecological plaque hypothesis (Marsh, 2003). ,
Prevention and treatment of periodontal diseases mainly focuses on the reduction of bacterial load. Conventional treatment modalities include surgical and non-surgical management which emphasizes on mechanical debridement, often accompanied by antibiotics. Due to the emergence of antibiotic resistance and frequent re-colonization of treated sites with pathogenic bacteria, probiotics have emerged in the field of periodontics. Probiotics is based on the concept of bacterial interference, whereby one microorganism can prevent and or delay the growth and colonization of another member of the same or different ecosystem.
| Evidence Supporting the Use of Probiotics in Gingivitis|| |
Krasse et al. 2006,  Riccia et al. 2007,  and Shimauchi et al. 2008  reported statistically significant decreases in gingival index when probiotic group was compared with baseline values. In contrast, the study by Staab et al. (2009)  probiotic group showed a statistically significant increase in gingival index.
Krasse et al. (2006) assessed the beneficial effect of Lactobacilli reuteri against gingivitis, at a dosage of 2 × 10 8 CFU/day for 2 weeks. L. reuteri can act by the following three mechanisms:
- L. reuteri is known for the secretion of two bacteriocins, reuterin and reutericyclin, that inhibit the growth of a wide variety of pathogens.
- L. reuteri has a strong capacity to adhere to host tissues, thereby competing with pathogenic bacteria and
- The recognized anti-inflammatory effects of L. reuteri on the intestinal mucosa, leading to inhibition of secretion of proinflammatory cytokines, could be the foundation for a direct or indirect beneficial effect of this bacterium on patients with periodontal disease.
In the study by Twetman et al. (2009),  the authors observed that as soon as the probiotic (Chewing gums containing two strains of L. reuteri: ATCC 55730 and ATCC PTA 5289, 1 × 10 8 CFU/gum, to be chewed for 10 min daily for 2 weeks) intake was stopped, the percentage of sites that showed bleeding upon probing increased again.
| Evidence Supporting the Use of Probiotics in Periodontitis|| |
Among healthy individuals, the prevalence of lactobacilli (particularly Lactobacillus gasseri, Lactobacillus salivarius and Lactobacillus fermentum) and Bifidobacterium species were greater than in patients with chronic periodontitis. Studies suggest that lactobacilli residing in the oral cavity could play a role in oral ecological balance.
During the fermentation of 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 bone resorption associated with periodontitis.
Shimauchi et al. (2008)  analyzed salivary lactoferrin levels. The study showed that during the course of the study, for both the placebo as well as the probiotic (6.7 × 10 8 CFU of L. salivarius tablets three times daily for 8 weeks) group, salivary lactoferrin levels decreased significantly from baseline values.
In the study done by Teughels et al. (2007),  where no oral hygiene was performed, multiple applications of S. salivarius, Streptococcus mitis and S. sanguinis resulted in significant microbiological changes in sub-gingival plaque. In comparison with scaling and root planning alone, multiple sub-gingival applications of S. salivarius, S. mitis and S. sanguinis after root planning, resulted in significant additional microbiological reductions in anaerobic bacteria, in Porphyromonas gulae, in black pigmented bacteria and in P. intermedia, 12 weeks after root planning and without any form of oral hygiene. A statistically significant lower bleeding upon probing was observed for pockets that received multiple applications of probiotics, when compared with pockets, where scaling and root planning was done alone (30% vs. 45%, respectively). In this 12-week study, no oral hygiene was provided to the dogs.
Mayanagi et al. (2009)  reported that the periodontopathogenic bacteria in the probiotic group (the test group received 2.01 × 10 9 CFU/day of L. salivarius WB21 and xylitol in tablets for 8 weeks) were significantly decreased in sub-gingival plaque after 4 weeks of probiotic usage and tended to be lower after 8 weeks when compared with the placebo group. The authors calculated that the odds ratio for a reduction of Tannerella forsythia in the probiotic group was significantly increased over the course of the study compared with the placebo group.
When combining the microbiological effects for L. salivarius TI 2711 (tablet form) on untreated periodontitis patients, it has been shown that this probiotic could reduce the salivary black pigmented bacteria levels. , showed that this probiotic could reduce the salivary black pigmented bacteria levels. Additionally, when compared with a placebo treatment, additional sub-gingival reductions in P. gingivalis levels could be achieved. A species-specific antimicrobial activity was also observed by Kõll-Klais et al.,  with facultative heterofermentative lactobacilli being the strongest inhibitors of A. actinomycetemcomitans, P. gingivalis and P. intermedia.
Staab et al. (2009),  investigated the effects of a commercially available probiotic milk containing L. casei Shirota on gingival health. The test group drank a probiotic drink once a day for 8 weeks; the control group did not receive any product to drink. They also analyzed, the amount of interproximal plaque and plaque index, the papillary bleeding index and polymorphonuclear elastase, myeloperoxidase and matrix metalloproteinase-3 in GCF. At the end of this 8-week study, elastase activity and matrix metalloproteinase-3 was significantly lower in the probiotic group when compared with the control group.
In the 4-day study of Riccia et al. (2007),  using a Lactobacillus brevis (CD2) lozenge once daily, on untreated periodontitis patients, significant decreases were seen in nitrite/nitrate, prostaglandin E 2 , matrix metalloproteinase and interferon-gamma levels in saliva of the probiotic group at the end of the study.
Nackaerts et al. (2008)  analyzed radiologically the alveolar bone around the teeth that received the positive control treatment and the alveolar bone around the teeth that received root planning and repeated sub-gingival application of the bacterial mixture. These authors observed that the bone density within periodontal pockets treated with beneficial bacteria improved significantly after 12 weeks, while this improvement was not statistically significant for the positive control pockets.
| Residence Time of Probiotics in Oral Cavity|| |
Residence time of probiotics in oral cavity after treatment withdrawal was studied by Çaglar et al. (2005). A reduced S. mutans level was shown after a 2-week use of a L. reuteri-enriched yogurt; effects were observed during use and for a few days after discontinuation. A loss of L. reuteri colonization was observed that two months after having discontinued probiotic use. Permanent colonization of probiotic bacteria in oral cavity is unlikely and it has suggested the use of probiotic on a regular basis. ,
Latency time of probiotics was assessed in oral cavity areas. Probiotic could be found on oral mucous membrane, tongue and in stimulated saliva for more than 3 weeks. And S. salivarius K12 had gradually reduced 8 days after treatment withdrawal. 
| Safety Aspects|| |
Although no serious adverse events have been described in clinical trials, systemic infections associated with specific probiotics have been noted. Major and minor risk factors for probiotic-associated sepsis have been identified. Major risk factors include immunosuppression (including a debilitated state or malignancy) and prematurity in infants. Minor risk factors are the presence of a central venous catheter, impairment of the intestinal epithelial barrier (such as with diarrheal illness), cardiac valvular disease (Lactobacillus probiotics only), concurrent administration with broad-spectrum antibiotics to which the probiotic is resistant and administration of probiotics via a jejunostomy tube. Therefore, Boyle et al. (2006) recommend that probiotics should be used cautiously in patients with one major risk factor or more than one minor risk factor. 
Probiotics can alter the immune response to vaccines. There is evidence that some specific probiotics can alter monocyte and natural killer cell function in the blood. Evidence is also accumulating that taking some specific probiotics can boost antibody responses to oral and systemically administered vaccines. This area needs further investigation.
| Conclusion|| |
The probiotics are body's own resident flora so are most easily adapted to host. With fast evolving technology and integration of biophysics with molecular biology, designer probiotics poses huge opportunity to treat diseases in a natural and non-invasive way. Probiotics might offer opportunities to manipulate the oral microbiota or, albeit more limited, periodontal health by either direct microbiological interactions or by immunomodulatory interactions. Genetically modified microbes bring a new dimension to the concept of probiotics. Their main thrush is on reducing the harmful properties of pathogenic strains naturally colonizing the oral cavity. The modified strain could then be used to replace the original pathogen. Also, they could be used to enhance the properties of a potentially beneficial strain. In the field of oral immunology, probiotics are being used as passive local immunization vehicles against periodontal diseases. Advances and accomplishments attained give us the ability to employ these friendly bacteria (probiotics) as 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.
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