|Year : 2016 | Volume
| Issue : 1 | Page : 36-41
Implications of Probiotics on Oral Health: Past-to-Present
Archana Muralidhar Menon
Department of Periodontics, Nair Hospital Dental College, Mumbai, Maharashtra, India
|Date of Web Publication||12-Apr-2016|
Archana Muralidhar Menon
Department of Periodontics, Nair Hospital Dental College, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Misuse of antibiotics has led to an exponential increase in cases related to antibiotic resistance. This alarming situation calls for antibiotic substitutes to restore sound health. The answer to this is "PROBIOTICS." Considered inimical to pathogens, probiotics help the commensal microflora residing in the host's body to combat diseases. It increases the number of good microorganisms to fight the bad ones. Traditionally considered beneficial against gastrointestinal problems, probiotics in recent times has showcased its ability to take down oral pathogens as well. The aim of this article is to review the literature till date to (1) understand the evolution of probiotics, (2) assess its impact on potential oral pathogens, and (3) analyze its significance in establishing good oral health.
Keywords: Caries, oral health, periodontal diseases, probiotics
|How to cite this article:|
Menon AM. Implications of Probiotics on Oral Health: Past-to-Present. J Dent Res Rev 2016;3:36-41
| Introduction|| |
Antibiotics have in recent times registered an increase in the number of individuals facing antibiotic resistance, purely due to its fraudulent use. Antibiotic resistance is like a ticking time bomb that needs attention similar to terrorism. This urgency has brought the medical fraternity to use "PROBIOTICS," which are microorganisms introduced in the body for its beneficial qualities. Their ability to fight infections supersedes that of antibiotics as they are a healthier alternative to the latter. Since its conception in 1953, probiotics have evolved till date.
| History and Development of Probiotics|| |
There has been a lot of confusion regarding the derivation of the name. It was believed to be purely a Greek derivation of two words, ∏PO +βίoς, i.e.,' For Life'. However, ∏PO in Greek means "before," whereas in Latin, this preposition means "for." Hence, the name "probiotic" is recently known to be derived from "pro," in Latin (for) and' βίoς', in Greek (life).  The term "probiotic" was first used by Kollath (1953).  Since then, a number of definitions have been devised for probiotics [Table 1] and the final definition given by Fuller was adopted in 2004.
Historic evidence states that microorganisms played an important role in improving human health since long. In 76 B.C., Roman historian Phlinius suggested the use of fermented dairy products to treat gastroenteritis.  In 7000 B.C, Egyptians consumed "Laban Rayeb" and "Laban Khad" (fermented milk products) that proved beneficial. Tissier (1900) isolated a bifidobacteria "Bacillus bifidus0" from the stools of children suffering from diarrhea and observed that these bacteria were in abundance in healthy children. In 1908, he found that they were present in the oral cavity of breastfed infants and recommended their administration to infants suffering from diarrhea to negate the action of putrefactive bacteria. In 1907, Elie Metchnikoff observed the lives of Bulgarian peasants and claimed that the intake of lactic acid containing yogurt increases the longevity of the host. In 1905, Stamen Grigorov isolated an organism called, "Lactobacillus bulgaricus" (now called Lactobacillus delbrueckii subsp. bulgaricus) from the Bulgarian yoghurt. In 1921, Rettger and Cheplin demonstrated the predominant existence of "Lactobacillus acidophilus0" in the human intestine and concluded it to be the microbe of the gut. In 1917, breaking the myth that only lactobacillus and bifidobacteria are capable of combating pathological gut flora, Nissle implanted "Escherichia coli" against Salmonella and Shigella. Minoru Shirota in the 1930's isolated "Lactobacillus casei0" and commercialized its use. In 1985, Gorbach and Goldin isolated "Lactobacillus rhamnosus GG" from the intestinal tract of a human. This strain was the first to get the most clinical attention.  Apart from bacteria, saprophytic yeasts have also shown the potential to be used as probiotics. "Saccharomyces boulardii," proved useful in the treatment of gastroenteritis in children.  Since then, a large number of microorganisms have been recognized to be used as probiotics, illustrated in [Table 2].
| Criteria for Selection of Probiotics|| |
In order to be used commercially, there are certain criteria that have to be met by probiotics which are as follows:
- Should be of host origin
- Possess phenotype and genotype stability
- Proliferation in large numbers
- Viable during processing and storage
- Nonpathogenic and nontoxic
- Resist low pH and acidity
- Ability to colonize in the target spot
- Antimicrobial activity against potential pathogens
- Ability to reduce surface adhesion of pathogens
- Ability to elicit host's immune response against harmful bacteria
- Influence local metabolic activities. 
| Sources of Probiotics|| |
Probiotics are available in medicinal preparations or in functional foods. Medicinal preparations are available as mouth rinses, tablets, and lozenges. In functional foods, they are present in any of the following forms:
- Culture concentrations added to beverages like juices
- Inoculated in prebiotic fibers
- Inoculated in dairy products
- Concentrated and dry cells such as dietary supplements - capsules, tablets or powder
- Fermented nondairy products such as kimchi and kombucha.
LAB strains are most commonly used as commercial probiotics, of which lactobacilli and bifidobacteria top the list; illustrated in [Table 3].  Production of commercial probiotics is in its infancy stage in India, yet the country boasts of certain products that have earned recognition globally [Table 4]. 
| Mechanism of Action of Probiotics in the Oral Cavity|| |
For the effective functioning of probiotics, it is necessary that it survives in the oral cavity for a longer duration. For this, probiotics should successfully adhere to the surfaces of the oral cavity. Pretreatment with lysozymes has known to increase the adhesion of lactobacilli in a saliva coated surface without compromising on its viability. Aggregation with oral bacteria is also considered beneficial to improve the survival rates of probiotics. L. salivarius W24 was unable to survive alone, but when introduced with commensal microorganisms, it showed promising results. Similarly, L. plantarum SA-1 and L. rhamnosus ATCC 7469 formed substantial biofilms when co-cultured with Actinomyces naeslundii.  The exact mechanism of action of probiotics in the oral cavity is unclear. Yet, they are assumed to function in the following ways: ,
- Competing for growth factors, nutrients, and adhesion sites: L. rhamnosus GG, L. acidophilus, L. casei, and L. reuteri competitively inhibit Streptococcus mutans whereas L. rhamnosus GG inhibits Candida albicans
- Co-aggregation: Aggregation with oral commensals changes the composition of biofilms and prevents caries and periodontal diseases. Co-aggregation with pathogens restricts their actions and facilitates their removal. L. casei, L. rhamnosus, L. acidophilus co-aggregates with Fusobacterium nucleatum, whereas heterofermentative lactobacilli co-aggregates with Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia.
Production of metabolites against pathogens
Antimicrobial substances such as organic acids, hydrogen peroxide, bacteriocin, ammonia, carbon peroxide, and diacetyl are produced by probiotics to eliminate pathogens. Weissella cibaria secretes hydrogen peroxide against Gram-positive bacteria. L. reuteri secretes bacteriocins such as reuterin and reutericyclin.
Enzymes produced by probiotics inhibit formation of harmful metabolites by pathogens. Lactobacillus brevis produced Arginine deiminase that prevented the formation of nitrite/nitrate in periodontitis patients.
Decreasing the secretion of proinflammatory cytokines, stimulating innate immunity to produce IgA, decreasing matrix metalloproteinase production, and stimulating phagocytes seems to be the action of probiotics to maintain the integrity of the oral epithelium. Reduction in the number of proinflammatory cytokines, interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-8 was noticed in the gingival crevicular fluid after consumption of a chewing gum with L. reuteri.
| Benefits of Probiotics|| |
Probiotics are known to benefit both general and oral health of humans.
Its oral implications are witnessed in the following:
- Dental caries
- Periodontal diseases
| Dental Caries|| |
The occurrence of dental caries is primarily attributed to S. mutans. Its exceptional ability to break down sugars faster and to produce water-insoluble polysaccharides renders it dangerous. Several studies have been carried out to comprehend the action of probiotics on S. mutans.
- Studies involving lactobacilli: Nδse et al. administered probiotic milk with L. rhamnosus GG to children between the ages 1-6 years, 5 days a week for 7 months. Reduced levels of S. mutans were noted at the end of the trial.  Caglar et al. carried out trials with L. reuteri ATCC 55730, L. reuteri ATCC PTA 5289 and observed a reduction in the levels of S. mutans. Haukioja et al. (2008) demonstrated the ability of L. casei ATCC 11578 to decolonize and prevent the adhesion of S. mutans to saliva-coated hydroxyapatite. Chuang et al. observed reduced levels of S. mutans, 2 weeks posttrial with Lactobacillus paracasei GMNL-33.  Campus et al. administered L. brevis CD2 lozenges to high-risk caries children (aged 6-8 years) for 6 weeks and noted a decrease in the levels of S. mutans
- Studies involving bifidobacteria: Caglar et al. found reduced levels of S. mutans following a double-blind, randomized crossover trial, wherein 200 g of probiotic yoghurt with Bifidobacterium animalis susp. lactis-DN173 010 was administered to adults 
- Others: Kang et al. in an in vitro/in vivo study observed that strains of W. cibaria (CMS 1 and CMS 3), inhibited the formation of S. mutans biofilm.  Suzuki et al. in an in vitro study in Japan noticed that Enterococcus faecium WB2000 inhibited the formation of S. mutans biofilm. 
| Periodontal Diseases|| |
Periodontal pathology is mainly caused by A. actinomycetemcomitans, F. nucleatum, P. gingivalis, P. intermedia, Treponema denticola, and Tannerella forsythia. Various studies carried out have managed to establish the influence of probiotics on periodontal health.
- Studies involving lactobacilli: Vivekanand et al. observed a reduction in plaque accumulation, decreased bleeding on probing, and improvement in the existing condition of patients after the administration of L. reuteri probiotics.  Shimauchi et al. demonstrated an improvement in the clinical parameters of periodontitis patients, especially smokers, owing to the administration of L. salivarius WB21 tablets.  Application of periodontal dressing with L. casei 37 cell suspension (108 cells/ml) and collagen in chronic periodontitis patients, reduced the levels of Bacteroids, Actinomyces, Staphylococcus intermedius, and C. albicans in periodontal pockets 
- Others: Tsubura et al. proved the efficacy of a mouth rinse containing Bacillus subtilis E-300 by showing an improvement in the gingival index and reduction in the number of periodontal pathogens in patients.  Toiviainen et al. (2015) administered lozenges with L. rhamnosus GG and B. animalis subsp. lactis Bb-12 for 4 weeks and demonstrated a decreased plaque and gingival index in adults. 
| Halitosis|| |
Halitosis or oral malodor is caused by the production of volatile sulfur compounds (VSC) such as hydrogen sulfide, methylmercaptan, and dimethyl sulfide due to the degradation of sulfur containing amino acids by Gram-negative anaerobic bacteria. These bacteria include F. nucleatum, P. gingivalis, P. intermedia, and T. denticola. Halitosis is attributed to the imbalance in the levels of oral commensals.
Henker et al. investigated a 9½-year-old girl who suffered from halitosis due to intestinal gases. Administration of Mutaflor (E. coli Nissle 1917 probiotic) brought about an improvement in her condition owing to the reduction of VSC production.  Kang et al. tested children suffering from halitosis. Mouth rinse containing W. cibaria was given, and a reduction in VSC production by F. nucleatum was noted due to the antagonistic action of hydrogen peroxide (metabolite of W. cibaria).  Iwamoto et al. studied the action of L. salivarius WB21 on halitosis. Tablets of the Lactobacillus strain and xylitol were administered for 4 weeks and an improvement in halitosis and decreased bleeding on probing was noticed. 
| Candidiasis|| |
Candidiasis is commonly seen in elderly and in immunocompromised patients, which is caused by C. albicans. Hatakka et al. in 2007, performed a 16-week, randomized, double-blind, placebo-controlled study where a probiotic cheese with L. rhamnosus GG and Propionibacterium freudenreichii susp. shermanii JS was administered. This trial demonstrated a significant reduction in the number of C. albicans.  Dos Santos et al. observed decreased levels of C. albicans after the administration of probiotic Yakult LB (L. casei and Bifidobacterium breve) for 20 days to individuals suffering from oral candidiasis. 
| Aids|| |
Studies carried out by Lin Tao et al. in 2008 suggest slow progression of AIDS due to the lactobacilli strains that bind to mannose found on HIV envelope. This binding causes the colonization of HIV and prevents its further spread. 
| Safety and Dosage|| |
According to the U.S. Food and Drug Administration, probiotic strains have to meet certain criteria to be Generally Recognized as Safe (GRAS), which are as follows:
- Should not cause systemic infections
- Should not induce antibiotic resistance in pathogens
- Should not cause deleterious metabolic activities and excessive immune stimulation.
Lactobacilli and bifidobacteria rarely cause infections, so they easily come under GRAS category. But, Bacillus, Enterococcus, and Streptococcus groups possess strains capable of infecting humans. Hence, careful analysis should be carried out before using potential probiotic strains belonging to these genera commercially.
Regarding dosage, there is no standard dosage recommended for the administration of probiotics. Studies carried out showed a wide range of dosages that are safe for various probiotics. For lactobacilli, dosages ranged from 100 million to 1.8 trillion colony-forming units per day. Saccharomyces dosages ranged between 250 mg and 500 mg/day. Variations are seen in dosages depending on the age, where dosages for children are typically half the adult dose and for infants, it is one-fourth the adult dose. 
| Side-Effects|| |
In spite of being considered "safe," certain strains of lactobacilli and bifidobacteria have been associated with infections following their consumption, in addition to other probiotic microorganisms. The observed side-effects are as follows:
- Bacteremia and Endocarditis: Reported generally in patients who are immunocompromised or have systemic disorders
- Associated with L. rhamnosus GG, L. plantarum, L. casei, L. paracasei, L. salivarius, L. acidophilus, E. faecalis, E. faecium, bifidobacteria, Lactococcus lactis, Leuconostoc, and Pediococci species
- Several cases are reported against B. subtilis
- Septicemia: Reported with L. rhamnosus GG, which caused liver abscess following dental treatment
- Fungemia: Associated with S. boulardii. Some patients developed septic shock following the infection. It was mostly noticed in critically-ill/immunocompromised patients
- Nosocomial infections and Vancomycin resistance: Increased risks have been associated with enterococci species
- Development of caries: Certain strains of lactobacilli along with S. mutans have shown the potential to play a significant role in the progression of dental caries. The production of organic acids by the lactobacilli ssp. against pathogenic microbes seems to be the culprit. Associated strains include L. salivarius W24, L. salivarius LS 1952R, L. plantarum 299v, and L. plantarum 931. 
However, as adverse effects following consumption are noticed by far mostly in immunocompromised or critically-ill patients, probiotics available commercially can be regarded safe to a greater extent.
| Conclusion|| |
Probiotics hold promise in improving oral health. Nevertheless, more long-term clinical trials are required to understand its functioning and to substantiate its effects on the body. Research is being carried out to ascertain its use as periodontal and/or caries vaccine and for the prevention of cancer. There is a need to discover more "safe" microorganisms with probiotic potential in the light of antibiotic resistance. Let us hope that incessant studies in the field of probiotics render it as a permanent treatment modality rather than an adjunct in the treatment of oral diseases.
| Acknowledgment|| |
The author expresses sincere thanks to Dr. Praneeta Kamble, Associate Professor, Department of Periodontics, Nair Hospital Dental College, for the valuable support and guidance through the various stages of manuscript preparation.
Financial Support and Sponsorship
Conflicts of Interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]