Untitled Document

Prebiotics and Probiotics: Role in prevention and cure of
human systemic and oral diseases – A review

Sadanandan Sowmya1, Setty Suhas2*
1Senior Lecturer, Department of Periodontics, Hasannamba Dental College and Hospital, Hassan-573201, Karnataka
2* Professor and Head,  Department of Oral Medicine and Radiology, Sri Siddhartha Dental College, Sri Siddhartha Academy of Higher Education, Tumkur-572107, Karnataka

Year : 2021 | Volume : 4 | Issue : 1 | Page : 3 | DOI -10.46319/RJMAHS.2021.v04i01.002

Prebiotics and probiotics, are revolutionary medical discoveries which have made a big impact in human disease management. Probiotics are dietary supplements containing potentially beneficial bacteria or yeasts. They promote healthy flora and suppress pathogens. Hence incorporating probiotics in diet could effectively help to stop, retard, or even delay the pathogenesis of many diseases, including those of the oral cavity. With the emergence of new microbial infections, prebiotics and probiotics offer a paradigm shift to traditional treatment approach from eliminating specific microbe to altering microbial ecology.  This paper reviews the history of probiotics, mechanism of action, and the current scenario in applying probiotics for the prevention or treatment of oral diseases and also covers pertinent literature on its use in managing systemic diseases including COVID-19.
Keywords:  oral disease, systemic disease, management, Lactobacillus, Bifidobacterium, oral flora

The number of diverse microorganisms colonizing the human body out number its cells by upto a 100 times. Microbial dysbiosis in the body is invariably associated with a disease, however the concept of 'bacteriotherapy' for health benefit has off late gained much attention. The term probiotic is derived from Latin (pro) and Greek (bios) meaning literally “for life”. Probiotics were then defined by FAO/WHO (The Food Agricultural Organization/World Health Organization) as live microorganisms which when administered in adequate amounts (in food or as a dietary supplement) confer a health benefit on the host improving microbiological balance in the intestinal tract. Probiotic bacteria are broadly categorised into two genera Lactobaccilus and Bifidobacterium. The other microorganisms classified into this group are yeast and molds.[1-3]

Historical perspective
The history of probiotics is as old as human civilization itself. The concept of probiotics was popularized during early 1900s with pioneering efforts of Nobel laureate Ilya Ilyich Metchnikoff. He observed the benefits of ingestion of yoghurt which contained large quantities of Lactobacillus species. In 1907, based on his findings Metchnikoff wrote his famous text, “The Prolongation of Life” later, in 1908, he was awarded the Nobel Prize in Medicine for his contributions to immunology which paved the way for the present day probiotics.
The term probiotics as “growth promoting factors produced by microorganisms” was introduced by Lilley and Stillwell in 1965. Later in 1984 Hull identified the first probiotic species, the L. acidophilus.  In 1991 B. bifidum was identified by Holcombh. The present usage of the term probiotic was proposed by Roy Fuller. Currently followed definition of probiotics was formulated in 2001 by FAO/WHO.[1, 2]
Mechanism of action
Some of the potential general mechanisms (Figure 1) are: modulation of the immune system, competitive adherence to the mucosa and epithelium, secretion of antimicrobial substances, strengthening of the gut epithelial barrier, compete for nutrients that would otherwise be utilized by pathogens. The exact mechanism still is not very well understood.
General medical applications
Conditions like antibiotic-associated diarrhea, acute infectious diarrhea, necrotizing enterocolitis and infant colic have shown to be effectively treated with probiotics.[3] Recently studies have even reviewed the possible benefits of probiotics in reducing the incidence and severity of Covid-19.[8]  A summary of applications is shown in table 1.
Table 1. General medical application of probiotics

Disease condition

Probiotic  Strain/ Ref


Respiratory tract infections
And Pneumonia (Relevance to COVID-19)


  • Antibiotic-associated diarrhea
  • Traveler’s diarrhea
  • Rotavirus diarrhea

L.gasseri, L.casei, B.longum
B.breve  and B.bifidum[8]


L. GG[9]



S. boulardi , L. acidophilus , B. bifidum[10]
L. rhamnosus and L. reuteri[11]

Lowering duration and severity
of flu-like illness. Lower
incidence of ventilator associated pneumonia
Reduced the recurrence rate of Clostridium difficile, with disappearance of abdominal cramps and diarrhea


Had a significant effect

Reduced diarrhea much earlier than  placebo group


L. delbrueckii subsp. bulgaricus, Lactococcus lactis[12]

Lactococcus lactis[13]

B. adolecenti ATCC 15703 , L. plantarum ATCC 8014 ,L. plantarum ATCC 8014[14]

Exhibited an antimutagenic activity


Decreased mutagenic substances

Reduced 48.7%,59.37%,54.64% on tested mutagenic substance

Irritable Bowel Syndrome(IBS)

B. longum LA 101, L. acidophilus LA 102, Lactococcus lactis LA 103, St. thermophilus LA 104[15]

Relief of overall IBS symptoms and  abdominal discomfort

Inflammatory bowel disease (IBD)

E. coli Nissle 1917[16]



Helped in maintenance of remission in ulcerative E. colitis patients

Reduced the risk of relapse of Crohn’s disease

Helicobacter pylori

 S. boulardii[18]

Meta-analysis  reported increased  eradication rate and reduced the risk of overall H. pylori therapy-related adverse effects

 Urinary tract infections

L. fermentum[19]

 Probiotics was effective when combined with  low doses of ampicillin in animals

Reduction in serum cholesterol

L.plantarum 299v[20]

Bifidobacterium bifidum Bifidobacterium lactis, Lactococcus lactis [21]

Decreased  serum LDL cholesterol

Preventive effect on the incidence of eczema in high‐risk children

Application of probiotics in oral diseases
Probiotics are widely used to treat gastrointestinal disorders, as mouth represents the beginning of the oral cavity, so gut health should essentially starts with the oral cavity. Due to many health benefits, probiotics are now widely used in dentistry. An ideal probiotic strain should have properties like non toxic, non-pathogenic, human origin with good shelf life and must replace and reinstate the normal microflora.[3]
 Probiotics in dental caries
Dental caries is a multifactorial disease with complex interaction among plaque microorganisms, diet, and host factors. Streptococcus mutans which acts by destroying tooth enamel is long recognized as the main etiological agent for dental caries. Probiotic and molecular genetic techniques have been developed to replace cariogenic organisms with strains of bacteria that are not cariogenic. Probiotic strains like Lactobacilli and Bifidobacteria are shown to be effective in caries prevention.
Meurman et al. was the first researcher to investigate homofermentative (cannot ferment sucrose or lactose)lactobacillus strain, L. rhamnosus CG  against caries pathogens.[22] Hillman and  coworkers tested a non-acid producing S. mutans strain that produces a bacteriocin against other S. mutans strains in the oral cavity to replace the naturally occurring cariogenic strains.[23]  The pathogenicity of  S. mutans and S. sorbinus is related to their acidogenic potential and ability to form water-insoluble extracellular and enzymatically undegradable polysaccharides from sucrose. These polysaccharides help in the adhesion and colonization of cariogenic organisms and mediate protection against antimicrobial agents and resistance to toxic compounds. Synthesis of these glucans is via glucosyltransferase B, glucosyltransferase C and glucosyltransferase D genes. Hence genetically mutated strains lacking the ability to metabolize fermentable carbohydrates to organic acids have been developed. One such variant is S. mutans with a glucosyltransferase C (gtf C) gene mutation. The mutated gtfC gene that affects the ability of S. mutans to produce extracellular glucans resulted in decreased extracellular matrix component of mixed oral biofilms from 51 to 33% of the biofilm volume. The reduction of the number of mutans streptococci in saliva with probiotic containing lactobacilli or bifidobacteria is also reported by Ahola et al .[24]
L reuteri is an obligate heterofermentative resident of the human gastrointestinal tract. L.reuteri produces reuterin  and reutericyclin  which are water-soluble, broad-spectrum antimicrobial compounds exhibiting antagonistic activity. The effect of L. reuteri has also been tested for its caries-preventing effects. It was seen that eating L. reuteri containing yogurt daily for 2 continuous weeks reduced the S.mutans levels in saliva by 0.5 log10 colony-forming units. The reduced S. mutans levels were maintained for at least up to 2 weeks after discontinuing the consumption.[25] There are several other reports of reduction in mutans streptococci levels in saliva with the use of probiotic-containing yoghurts.[26]
Probiotics delivered through tablet, chewing gums have also been tested. Caglar et al. studied the effect of L.reuteri ATCC 55730 containing straw or tablets on the level of S.mutans and lactobacilli in the saliva of adults. Probiotic consumption showed significant reduction in S.mutans levels.[27] Studies focused on caries prevention till now have utilized bacteria that expressed bacteriocins or bacteriocin-like inhibitory substances, recombinant  and genetically modified strain and strains with suitable antagonistic activity against relevant oral bacteria. Although probiotics seems to be promising in caries prevention, but recent meta-analysis suggest further studies to ascertain its efficacy.[28]
Probiotics in periodontitis
Periodontitis is a chronic inflammatory disease caused by a combination of specific bacteria and inflammatory host responses and resulting in the destruction of the connective tissue of the gingiva, periodontal ligament and alveolar bone. It has a complex multifactorial etiology with the plaque biofilm having a key role. The disease is associated dysbiosis in the host’s local microbiome with elevated numbers and proportions of bacterial species designed as ‘pathogens’ and reduced proportions of bacteria associated with health. The beneficial bacteria may modulate the host response and correct the bacterial imbalance and may therefore considered as a preventive or treatment option for periodontitis.
The current evidence recommend the use of probiotics for managing gingivitis or periodontitis.[28] The first studies of the use of probiotics for enhancing oral health were for the treatment of periodontal inflammation.[29]  Studies have suggested lactic acid inhibition of oral bacteria could be helpful in treating periodontal diseases. Periodontitis patients using probiotic chewing gum or lozenges saw significant improvement in their periodontal status. In a parallel, double-blind, randomized, placebo-controlled study by Krasse et al.  the effects of L. reuteri on 59 recurrent gingivitis patients were tested.  L. reuteri strains were administered via chewing gum twice a day for 2 weeks at a concentration of 1×10 8 CFU (colony forming unit) along with scaling and root planning. After 2 weeks better improvement was noted in the group consuming probiotic chewing gum.[30] Koll-Klais et al. in a study found a higher prevalence of lactobacilli, particularly L. gasseri and L. fermentum in the oral cavity of healthy subjects than patients with chronic periodontitis. This  higher lev­els of Lactobacillus in microbiota caused an 82% inhibition in Porphyromonas gingivalis and 65% inhibition in Prevotella intermedia growth.[31] Probiotic tablets containing L. salivaris T1 2711 strain were found to decrease bleeding on probing and Porphyromonas gingivalis count.[32] Similarly Kang et al. in a randomised double-blind, placebo-controlled trial showed the ability of Weisella cibaria  CMS1 containing mouth rinse to inhibit biofilm formation. The study subjects showed a significant reduction in plaque index reduction of about 20.7%.[33] Probiotic lozenges containing Lactobacillus brevis are effective in reducing salivary proinflammatory cytokines (prostaglandinE2, matrix metalloproteinases, and interferon γ) and the clinical parameters in chronic periodontitis subjects. The beneficial anti-inflammatory effects of L. brevis could be attributed to its capacity to prevent the production of nitric oxide. [34]
The idea of guided pocket recolonisation could be a novel treatment approach to treat periodontal diseases. Teughels et al. in an animal study with artificially induced pockets  reported that the subgingival application of a bacterial mixture containing sanguis KTH-4, Streptococcus salivarius TOVE and Streptococcus mitis BMS in artificially induced pockets  after scaling and rootplaning significantly delayed subgingival recolonization of periodontopathogens.[35] There are other favourable  reports of replacement therapy in delayed recolonisation due to plaque inhibition, anti-inflammatory, and antimicrobial effects of probiotic strains.[36]  Volozhin et al. demonstrated a considerable decrease in the number and frequency of isolation of aggressive microbial pathogens using L. casei 37 cell suspension containing periodontal dressing which  provided remission up to 10-12 months.[37] Grudianov et al. using a mixture of probiotics reported improvement of the clinical signs of gingivitis. Probiotics have also been employed as antimutagenic and anticarigenic agents.[38] Probiotic containing food offer great oral health benefits. In an epidemiological study, Shimazaki et al. found that individuals, regularly consuming yogurt or beverages containing lactic acid exhibited significantly lower prevalence of deep probing depth and severe clinical attachment loss than individuals who consumed few of these dairy products. However a similar effect was not observed with milk or cheese.[39] In another study Narva et al. reported L. helveticus fermented milk stimulate osteoblast and promote bone formation. This could be used to reduce and repair periodontal bone destruction.[40]
“PerioBalance” chewing gums marketed by Sunstar (Etoy, Switzerland) were the first probiotic gum formulated to combat caries and periodontal disease. Each dose of lozenge contains 2 strains of at least 2 × 108 living cells of L. reuteri Prodentis (L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289). Each lozenge has to be used every day, either after a meal or in the evening after brushing. “Prodentis” is also a lozenge containing L. reuteri shown beneficial in chronic periodontitis.[36] “PerioBiotic”(Designs for Health, Inc.,) toothpaste is another all-natural, fluoride-free oral hygiene supplement containing Lactobacillus paracasei probiotic. “Acilact” is another probiotic preparation with five live lyophilized lactic acid bacteria, which is claimed to improve both clinical and microbiological parameters in gingivitis and mild periodontitis patients.[41] Wakamate D (Wakamoto Pharmaceutical Co., Tokyo, Japan) containing 6.5x108 colony forming units (CFU) per tablet of Lactobacillus salivarius WB21 and xylitol (280 mg/ tablet) has also proved beneficial in improving periodontal parameters.These products should be studied further to draw a robust conclusion of their benefits.
 Probiotics in peri-implant disease
Peri-implant disease includes peri-implant mucositis, which is inflammation around the soft tissue without bone loss, and peri-implantitis having peri-implant bone loss along with soft tissue inflammation. It is treated by various ways and recently adjunctive probiotics have been tried with inconsistent results. Daily administration of a lozenge containing L. reuteri for 30 days along with mechanical debridement found improvement in clinical parameters in peri-implant mucositis and peri-implantitis.[42]  In contrast some reports show not much benefit.[43] Hence further studies are required to draw conclusive result.[44]
Probiotics in oral wound healing
Probiotics containing L. reuteri have shown to promote wound healing. Walivaara et al.  tested the effect of a lozenge containing two strains of  L. reuteri (DSM 17938 and ATCC PTA 5289) or placebo for two weeks after surgical removal of third molars. The study did not find any significant influence of probiotic supplements on objective wound healing but there was significant post-operative ameliorations in patients.[45] Further studies must be done to clarify the effects.
Probiotics and halitosis
Halitosis is the unpleasant odor emanating from the oral cavity.  It can be caused by respiratory tract infections, metabolic disorders, and consumption of some particular foods but the most common reason for halitosis is the imbalance of the normal microflora of the oral cavity which degrades proteins, blood, mucins, food debris to produce volatile sulphur compounds (VSC). Periodontal pathogens like Fusobacterium nucleatum(Fn), Porphyromonas gingivalis(Pg), Prevotella intermedia (Pi), Aggregibacter actinomycetemcomitans (Aa) and Treponema denticola (Td) produce VSC. The probiotic strain  W.cibaria, produces hydrogen peroxide which is antimicrobial in nature. Kang et al. reported the capacity of various strains of W.cibaria to inhibit the production of volatile sulphur compounds by F. nucleatum. The study found that gargling with a solution containing W.cibaria was associated with reduced hydrogen sulfide and methanethiol production and consequently a reduction in halitosis.[46]
 Various probiotics are marketed for the treatment of both mouth and gut-associated halitosis. The administration of probiotic lozenges containing Streptococcus salivarius K12 reported reduced levels of volatile sulphur compounds. Streptococcus salivarius produce bacteriocins that are antibacterial, thus reducing VSC production and halitosis.[47]
Probiotics in oral cancer, fungal infections and HIV
Probiotics are  proved beneficial in oral cancer treatment. A recent systematic review revealed ability of  L. salivarius REN to inhibit the development  oral carcinogenesis.[48] But currently, there is very minimal literature on oral carcinogenesis and requires further research. Several Candida species are known to cause fungal infection in the oral cavity.  Probiotic bacteria are effective against oral candida infections. Short-term consumption of cheese containing LGG and L. rhamnosus LC 705  in adults resulted in reduced salivary yeast count.[24] When a test group of elderly people consumed cheese containing L. rhamnosus strains GG and LC705 and Propionibacterium freudenreichii ssp. shermanii JS for 16 weeks, the number of oral yeast counts decreased, but no changes were observed in mucosal lesions.[49]  There are many works on the benefits of probiotics in HIV-associated gut dysbiosis, but recently probiotics were tried in modulation of dysbiotic salivary microbiota in HIV infection. The study results proved to have some beneficial effect in normalizing the dysbiotic oral flora in HIV subjects.[50] Hence  future studies are encouraged to draw further conclusion.
Probiotics in orthodontic treatment
Demineralization often occurs during fixed orthodontic treatment mainly due to the complex design of orthodontic bands and brackets. This creates a favorable environment for cariogenic mutans streptococci strains. A short term study by Cildir and coworkers found daily consumption of fruit yogurt with B. animalis subsp. Lactis DN -173010  reduced the salivary levels of mutans streptococci in patients with fixed orthodontic appliances. Hence this could be beneficial in preventing demineralization and white spot formation during orthodontic treatment.[51] Recently a systematic review showed a conflicting result on the benefits. Hence further studies are required to confirm the results.[52]
 Probiotics and voice prosthesis
There is no evidence of the effect of probiotics on dental restorations. However, benefits of probiotic in increasing life span of voice prosthesis is well documented. Buttermilk containing L. lactis and Lactococcus lactis ssp. cremoris and a fermented milk drink containing L. casei Shirota were examined both in vitro and in vivo studies found a decrease in the number of bacteria and yeast on voice prostheses and increased the lifetime of voice prostheses by four times.[53]
Probiotic preparation, dosage, and delivery modes
Probiotics include not just bacteria but also some fungi.  Many probiotics commercial products contain mixtures of two or more individual species. Few of the commonly used probiotic strains is listed in table 2.
Table 2. List of probiotic strain[3]



  • Lactobacillus rhamnosus GG
  • Lactobacillus reuteri
  • Lactobacillus casei
  • Lactobacillus paracasei
  • Bacillus coagulans
  • Bacillus clausii
  • Bifidobacterium infantis
  • Bifidobacterium longum
  • Bifidobacterium infantis
  • Streptococcus thermophilus
  • Escherichia coli strain
  •  Weissella sibaria
  • Saccharomyces boulardii
  • Saccharomyces cerevisiae
  • Aspergillus niger,
  • Aspergillus oryzae,
  • Candida pintolopesii,


Commercial preparations of probiotic supplements are available in freeze-dried (lyophilized) bacteria in powder, capsule, or tablet form. For oral use probiotics are incorporated in chewing gums, lozenges, gargling solution, and toothpaste. The dosage of probiotic foods and supplements depends upon the number of live organisms present in the product. For effective probiotic action 107and 1011 viable bacteria per day is recommended in various trials.
The required count of viable bacteria also varies with the transport medium used. Dairy medium requires100 times fewer viable bacteria than in a freeze-dried supplement to achieve similar numbers of live bacteria in the lower bowel.[4,49,54] Studies have evaluated effects of probiotics administered through different routes on oral pathogens (Table 3).

Table 3.  Details of the different delivery modes

 Delivery mode

                 Strain used



B. lactis Bb-12[26]

S. mutans ↓↓↓, lactobacilli↓↓↓


Prepared Straw/ Tablet

L. reuteri ATCC 55730 [27]


S. mutans ↓↓↓ ,lactobacilli -

Lozenge administered medical device
Ice cream

L. reuteri DSM17938,  L. reuteri ATCC PTA 5289 [36]


    B. lactis Bb-12[55]

   Aa, Pi, and Pg ↓↓↓



S. mutans ↓↓↓, lactobacilli –

 ↓↓↓ - significant reduction , - no change
 Prebiotic and probiotic food
Probiotics are not just commercially prepared but are naturally present in many foods. One of the most popular foods that contain probiotics is yogurt with live bacteria. The other dairy sources include aged, fermented cheese, buttermilk, dahi, koumiss and kefir. Kefir is a milk product made by combining milk and kefir grains. It contains probiotic bacteria and yeast.
Non diary sources include fermented vegetable dishes like Sauerruben (turnips) and sauerkraut (cabbage), which are popular in north Europe. Fermented vegetables are also widely used in Japan, China and Korea.  Sour pickles prepared using a solution of unrefined sea salt and clean, chlorine-free water are a good source of lactobacillus. Kombucha, a fermented tea thought to originate in China, is another great source of beneficial bacteria .
 Unlike probiotics which has viable microorganism “prebiotics” are nutrients that feed probiotic bacteria. The term ‘prebiotic’ was introduced by Gibson and Roberfroid.  Prebiotics consists of non-digestible food ingredients such as fructooligosaccharides (FOS), Lactulose, and inulin that are not destroyed while cooking. They beneficially affect the host by selectively stimulating growth and/ or increase the activity of a limited number of probiotic-like bacteria in a colon. The most common kind of prebiotic is fructo-oligosaccharide.“Synbiotic” is a combination of probiotics and prebiotics.[1,3,56]
Drug interaction
Probiotics generally have not shown to have many drug interactions. Some strains of L. acidophilus have shown to affect the metabolism of sulfasalazine, chloramphenicol palmitate, and phthalylsulfathiazole. Conversely, alcohol and antibiotics negatively affect Lactobacilli and bifidobacteria.[4,57]
Probiotics residence time in the oral cavity
Probiotic bacteria tend to colonize the oral cavity during active probiotic use. Horz et al.[58] assessed the latency period of probiotic Streptococcus salivarius K12, 4 tablets/day for 3 days in  the oral cavity in a 35-day follow-up. They found a gradual reduction in S. salivarius level beginning 8 days after treatment withdrawal. Several other studies have also reported reduced probiotic bacteria after discontinuation.[27] Permanent colonization of the probiotic may provide long-term benefit, but is unlikely in most cases.
 Safety and adverse reactions
Probiotics are generally found to be safe with minimal side effects. But there are reports of bacteremia and fungemia including sepsis, liver abscess, and endocarditis from L. GG in patients with severe illness. Most of the adverse events are seen in immunocompromised individuals.[59] The acidogenicity of lactobacilli and bifidobacteria cannot be ignored. In an animal model, L. salivarius strain was able to induce dental caries.[60] Secondly, the probability of risk of transferring antibiotic-resistance genes to pathogenic bacteria is another big concern. Hence probiotic therapy must be used cautiously especially in immunosuppressed subjects.
Probiotics are live microorganisms that when consumed in an adequate amount offer great overall health benefits. Probiotics have opened a new era in bacteriotherapy with the development of genetic engineering techniques, designer probiotics pose a huge opportunity especially in vaccine development to treat diseases in a natural and non-invasive way. Benefits of probiotics in the prevention or cure of many systemic diseases have been documented. In case of majorly occurring oral diseases (caries and periodontitis), they are caused due to ecological dysbiosis in the plaque biofilm. Hence probiotic bacteria are a great tool to modulate oral biofilm and prevent oral diseases. Although there is existing evidence on the benefits of probiotics in treatment or prevention of systemic and oral diseases, future studies on the use of probiotics should include systematic studies and randomized controlled trials in order to gain further insight into their safety, find new strains, understand their exact mechanism of action, determine dose and delivery modes to foster the development of novel preventive and curative treatment strategies.
1.    Gogineni VK, Morrow LE, Gregory PJ, Malesker MA.Probiotics: History and Evolution. J Anc Dis Prev Rem 2013;1: 1-7.
2.    Hamilton-Miller JM, Gibson GR, Bruck W. Some insights into the derivation and early uses of the word 'probiotic'. Br J Nutr. 2003 ;90:845.
3.    Chatterjee A, Bhattacharya H, Kandwal A. Probiotics in periodontal health and disease. J Indian Soc Periodontol. 2011;15:23-8.
4.    Hawrelak J, BNat(Hons). Probiotics. In: Pizzorno JE, Murray MT, editors. Textbook of Natural Medicine. 4th ed. St. Louis, Missouri: Churchill Livingstone Elsevier; 2013. p. 979–94.
5.    Mishra C, Lambert J. Production of anti-microbial substances by probiotics. Asia Pac J Clin Nutr. 1996;5:20-4.
6.    Iyer C, Kosters A, Sethi G, Kunnumakkara AB, Aggarwal BB, Versalovic J. Probiotic Lactobacillus reuteri promotes TNF-induced apoptosis in human myeloid leukemia-derived cells by modulation of NF-kappaB and MAPK signalling. Cell Microbiol. 2008;10:1442-52.
7.    Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003;52:827-33.
8.    Baud D, Dimopoulou Agri V, Gibson GR, Reid G, Giannoni E. Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic. Front Public Health. 2020;8;8:186.
9.    Pochapin M. The effect of probiotics on Clostridium difficile diarrhea. Am J Gastroenterol. 2000;95(1 Suppl):S11-3.
10.  McFarland LV. Meta-analysis of probiotics for the prevention of traveler's diarrhea. Travel Med Infect Dis. 2007;5:97-105.
11.  Rosenfeldt V, Michaelsen KF, Jakobsen M, Larsen CN, Møller PL, Tvede M, Weyrehter H, Valerius NH, Paerregaard A. Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers. Pediatr Infect Dis J. 2002;21:417-9.
12.  Hosono A, Sagae S, Tokita F. Desmutagenic effect of cultured milk on chemically induced mutagenesis in Escherichia coliB/r LWP2 trp-hcr. Milchwissenschaft 1986; 41: 142-5.
 13. Lankaputhra WE, Shah NP. Antimutagenic properties of probiotic bacteria and of organic acids. Mutat Res1998;397:169-82.
14.  Chalvo,V.I., Lingbeck, J.M., Kwon,Y.M., Ricke, S.C. Extracellular antimutagenic activities of selected probiotic Bifidobacterium and Lactobacillus spp. as a function of growth phase. Journal of Environmental Science and Health Part B 2008;43:193-8.
15.  Drouault-Holowacz S, Bieuvelet S, Burckel A, Cazaubiel M, Dray X, Marteau P. A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome. Gastroenterol Clin Biol. 2008;32(2):147-52.
16.  Kruis W, Fric P, Pokrotnieks J, Lukás M, Fixa B, Kascák M, et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004;53(11):1617-23.
17.  Campieri M, Rizzello F, Venturi A, Poggioli G, Ugolini F, Helwig U, et al. Combination of Antibiotic and Probiotic Treatment is efficacious in prophylaxis of post-operative recurrence of Crohn's Disease: A randomised controlled Study vs. Mesalazine. Gastroenterology 2000;118:A781
18.  Szajewska H, Horvath A, Piwowarczyk A. Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment. Aliment Pharmacol Ther 2010;32:1069-79.
19.  Silva de Ruiz C, López de Bocanera ME, Nader de Macías ME, Pesce de Ruiz Holgado AA. Effect of lactobacilli and antibiotics on E. coli urinary infections in mice. Biol Pharm Bull 1996;19(1):88-93.
20.  Naruszewicz M, Johansson ML, Zapolska-Downar D, Bukowska H. Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers. Am J Clin Nutr. 2002;76:1249-55.
21.  Niers L, Martín R, Rijkers G, Sengers F, Timmerman H, van Uden N,et al.The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy 2009;64:1349-58.
22.  Meurman JH, Antila H, Korhonen A, Salminen S. Effect of Lactobacillus rhamnosus strain GG (ATCC 53103) on the growth of Streptococcus sobrinus in vitro. Eur J Oral Sci1995;103(4):253-8.
23.  Hillman JD.Genetically modified Streptococcus mutans for the prevention of dental caries. Antonie Van Leeuwenhoek. 2002;82:361-6.
24. Ahola AJ, Yli-Knuuttila H, Suomalainen T, Poussa T, Ahlström A, Meurman JH,et al. Short-term consumption of probiotic-containing cheese and its effect on dental caries risk factors. Arch Oral Biol 2002;47(11):799-804.
25.  Nikawa H, Makihira S, Fukushima H, et al. Lactobacillus reuteri in bovine milk fermented decreases the oral carriage of mutans streptococci. Int J Food Microbiol. 2004;95(2):219-223.
25.  Nikawa H, Makihira S, Fukushima H, Nishimura H, Ozaki Y, Ishida K, Darmawan S, Hamada T, Hara K, Matsumoto A, Takemoto T, Aimi R. Lactobacillus reuteri in bovine milk fermented decreases the oral carriage of mutans streptococci. Int J Food Microbiol 2004 ;95:219-23.
26.  Zare Javid A, Amerian E, Basir L, Ekrami A, Haghighizadeh MH, Maghsoumi-Norouzabad L. Effects of the Consumption of Probiotic Yogurt Containing Bifidobacterium lactis Bb12 on the Levels of Streptococcus mutans and Lactobacilli in Saliva of Students with Initial Stages of Dental Caries: A Double-Blind Randomized Controlled Trial. Caries Res 2020;54:68-74.
27.  Caglar E, Cildir SK, Ergeneli S, Sandalli N, Twetman S. Salivary mutans streptococci and lactobacilli levels after ingestion of the probiotic bacterium Lactobacillus reuteri ATCC 55730 by straws or tablets. Acta Odontol Scand 2006;64(5):314-8.
28.  Gruner D, Paris S, Schwendicke F. Probiotics for managing caries and periodontitis: Systematic review and meta-analysis. J Dent. 2016;48:16-25.
29.  Kragen H.The treatment of inflammatory affections of the oral mucosa with a lactic acid bacterial culture preparation. Zahnarztl Welt 1954;9:306-8.
30.  Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G. Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri. Swed Dent J. 2006;30:55-60.
31.  Kõll-Klais P, Mändar R, Leibur E, Marcotte H, Hammarström L, Mikelsaar M. Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity. Oral Microbiol Immunol 2005;20:354-61.
32.  Matsuoka T, Sugano N, Takigawa S, Takane M, Yoshinuma N, Ito K, Koga Y. Effect of oral Lactobacillus salivarius TI2711 (LS1) administration on periodontopathic bacteria in subgingival plaque. J Jpn Soc Periodontol  2006;48(4):315–24.
33.  Kang MS, Chung J, Kim SM, Yang KH, Oh JS. Effect of Weissella cibaria isolates on the formation of Streptococcus mutans biofilm. Caries Res. 2006;40:418-25.
34.  Riccia DN, Bizzini F, Perilli MG, Polimeni A, Trinchieri V, Amicosante G,et al. Anti-inflammatory effects of Lactobacillus brevis (CD2) on periodontal disease. Oral Dis 2007;13(4):376-85.
35. Teughels W, Newman MG, Coucke W, Haffajee AD, Van Der Mei HC, Haake SK,et al. Guiding periodontal pocket recolonization: a proof of concept. J Dent Res. 2007;86:1078-82.
36.  Vivekananda MR, Vandana KL, Bhat KG. Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management of periodontal disease: a preliminary randomized clinical trial. J Oral Microbiol 2010;2:5344.
37.  Volozhin AI, Il'in VK, Maksimovskiĭ IuM, Sidorenko AB, Istranov LP, Tsarev VN,et al. Development and use of periodontal dressing of collagen and Lactobacillus casei 37 cell suspension in combined treatment of periodontal disease of inflammatory origin (a microbiological study). Stomatologiia (Mosk). 2004;83:6-8.
38.  Grudianov AI, Dmitrieva NA, Fomenko EV. Use of probiotics Bifidumbacterin and Acilact in tablets in therapy of periodontal inflammations. Stomatologiia (Mosk) 2002;81:39-43.
39. Shimazaki Y, Shirota T, Uchida K, Yonemoto K, Kiyohara Y, Iida M, et al.Intake of dairy products and periodontal disease: the Hisayama Study. J Periodontol 2008 ;79:131-7.
40.  Narva M, Halleen J, Väänänen K, Korpela R. Effects of Lactobacillus helveticus fermented milk on bone cells in vitro. Life Sci 2004 20;75:1727-34.
 41. Pozharitskaia MM, Morozova LV, Melnichuk GM, Mel’nichuk SS. The use of the new bacterial biopreperation Acilact in the combined treatment of periodontitis. Stomatologiia (Mosk) 1994;73:17–20.
42.  Galofré M, Palao D, Vicario M, Nart J, Violant D. Clinical and microbiological evaluation of the effect of Lactobacillus reuteri in the treatment of mucositis and peri-implantitis: A triple-blind randomized clinical trial. J Periodontal Res 2018;53:378-90.
43.  Hallström H, Lindgren S, Widén C, Renvert S, Twetman S. Probiotic supplements and debridement of peri-implant mucositis: a randomized controlled trial. Acta Odontol Scand. 2016;74:60-6.
44.  Silva AP, Cordeiro TO, da Costa RA, Martins ARLA, Dantas EM, Gurgel BCV, Lins RDAU. Effect of Adjunctive Probiotic Therapy on the Treatment of Peri-implant Diseases - A Systematic Review. J Int Acad Periodontol 2020;22:137-45.
45.  Wälivaara DÅ, Sjögren I, Gerasimcik N, Yucel-Lindberg T, Twetman S, Abrahamsson P. Effects of Lactobacillus reuteri-containing lozenges on healing after surgical removal of mandibular third molars: a randomised controlled trial. Benef Microbes. 2019;10:653-59.
46.  Kang MS, Kim BG, Chung J, Lee HC, Oh JS. Inhibitory effect of Weissella cibaria isolates on the production of volatile sulphur compounds. J Clin Periodontol. 2006;33:226-32.
47.  Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR. A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol 2006;100:754-64.
48.  Wan Mohd Kamaluddin WNF, Rismayuddin NAR, Ismail AF, Mohamad Aidid E, Othman N, Mohamad NAH, et al. Probiotic inhibits oral carcinogenesis: A systematic review and meta-analysis. Arch Oral Biol. 2020 Oct;118:104855.
49.  Hatakka K, Ahola AJ, Yli-Knuuttila H, et al. Probiotics reduce the prevalence of oral candida in the elderly--a randomized controlled trial. J Dent Res. 2007;86(2):125-130.
49. Hatakka K, Ahola AJ, Yli-Knuuttila H, Richardson M, Poussa T, Meurman JH, Korpela R. Probiotics reduce the prevalence of oral candida in the elderly--a randomized controlled trial. J Dent Res 2007;86:125-30.
50.  Jiménez-Hernández N, Serrano-Villar S, Domingo A, Pons X, Artacho A, Estrada V,et al.Modulation of Saliva Microbiota through Prebiotic Intervention in HIV-Infected Individuals. Nutrients 2019;11:1346..
51   .Cildir SK, Germec D, Sandalli N, Ozdemir FI, Arun T, Twetman S, Caglar E. Reduction of salivary mutans streptococci in orthodontic patients during daily consumption of yoghurt containing probiotic bacteria. Eur J Orthod 2009;31:407-11.
52.  Hadj-Hamou R, Senok AC, Athanasiou AE, Kaklamanos EG. Do probiotics promote oral health during orthodontic treatment with fixed appliances? A systematic review. BMC Oral Health 2020;20:126.
53.  Schwandt LQ, van Weissenbruch R, van der Mei HC, Busscher HJ, Albers FW. Effect of dairy products on the lifetime of Provox2 voice prostheses in vitro and in vivo. Head Neck 2005;27:471-77.
54.  Shornikova AV, Casas IA, Mykkänen H, Salo E, Vesikari T. Bacteriotherapy with Lactobacillus reuteri in rotavirus gastroenteritis. Pediatr Infect Dis J 1997;16:1103-7. doi: 10.1097/00006454-199712000-00002. PMID: 9427453.
 55. Caglar E, Kuscu OO, Selvi Kuvvetli S, Kavaloglu Cildir S, Sandalli N, Twetman S. Short-term effect of ice-cream containing Bifidobacterium lactis Bb-12 on the number of salivary mutans streptococci and lactobacilli. Acta Odontol Scand 2008;66:154-8.
 56. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 1995;125:1401-12.
57.  Pradhan A, Majumdar MK. Metabolism of some drugs by intestinal lactobacilli and their toxicological considerations. Acta Pharmacol Toxicol (Copenh) 1986;58:11-5.
58.  Horz HP, Meinelt A, Houben B, Conrads G. Distribution and persistence of probiotic Streptococcus salivarius K12 in the human oral cavity as determined by real-time quantitative polymerase chain reaction. Oral Microbiol Immunol 2007;22:126-30.
59.  Segarra-Newnham M. Probiotics for Clostridium difficile-associated diarrhea: focus on Lactobacillus rhamnosus GG and Saccharomyces boulardii. Ann Pharmacother 2007;41:1212-21.
60.  Matsumoto M, Tsuji M, Sasaki H, Fujita K, Nomura R, Nakano K, Shintani S, Ooshima T. Cariogenicity of the probiotic bacterium Lactobacillus salivarius in rats. Caries Res 2005;39:479-83.

Address for Correspondence: Dr. Suhas Setty, Professor and Head, Dept of Oral Medicine and Radiology, Sri Siddhartha Dental College,  Sri Siddhartha Academy of Higher Education, B H Road, Agalkote, Tumkur- 572107. E-mail:suhas.s@ssdctumkur.org


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Sri Siddhartha Medical College & Research Centre
Constituent College of Sri Siddhartha Academy of Higher Education
(Deemed to be University u/s 3 of UGC Act, 1956)
Accredited 'A' Grade by NAAC
Tumakuru, Karnataka, India. 572107

Research Journal of Medical and Allied Health Sciences is a medium for the advancement of scientific knowledge in all the branches of Medicine and Allied Sciences and publication of scientific research in these fields. The scope of the journal covers basic medical sciences, medicine and allied specialities, surgery and allied specialities, dentistry, nursing, pharmacy, biotechnology, public health and other branches of the allied health sciences. This journal is indexed with Advanced Science Index(ASI), National Science Library and Open J Gate.

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