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Oral Probiotics - Introducing Oraldiet® - an innovative oral probiotic lozenge containing Aloe Vera + Lactobacillus reuteri What is a probiotic? Elie Metchnikoff is regarded as the originator of the concept of probiotics. He was born in 1845 in the Ukraine and was a noted biologist, immunologist and Nobel Prize winner. Metchnikoff developed a theory that lactic acid bacteria in the GI tract could, by preventing peutrefaction, prolong life. Later, he simply stated that ‘Probiotics are viable bacteria that benefically affect the host by improving its intestinal microbial balance.’ Secondly, Charles Darwin, author of Survival of the Fittest, developed the word ‘fittest’ which meant ‘most suitable.’ Natural selection, according to Darwin, operates to produce individuals who are better adapted to their environment which, in microbial terms, was the ‘I’ view or planktonic phenotype. This was in contrast to Peter Kropotkin, who viewed the theory of Survival of the Fittest as supporting ‘cooperation’ rather than ‘competition.’ In his book Mutual Aid, A Factor of Evolution, he stated that the fittest was not necessarily the best at competing individually but often one of those best at working together in a community. Kroptokin was one of the original authors of the theme ‘We’ for the biofilm phenotype. The term ‘probiotic’ has had a colourful and varied definition. The Food and Agricultural Organisation of the UN and the International Scientific Assocation for Probiotics and Prebiotics give the best criteria: ‘Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit for the host.’ Today the ‘gold standard’ for demonstration of clinical efficacy in humans is the randomised double-blind placebo-controlled clinical trial. However, many ‘probiotics’ have never met those criteria in clinical trials. Human and veterinarian diseases for which probiotics have been evaluated The following is a list of systemic diseases and medical disorders where probiotic treatment has been successfully studied in clinical materials. • • • • • • • • • • • • Acute Diarrhoea Allergy/food allergy Antibiotic-associated diarrhoea Antimicrobial potential Atopy/atopic dermatitis Bacterial sepsis Bacterial vaginosis Cancer risk reduction Cardiovascular disease Clostridium difficile infection Colitis Crohn’s disease • • • • • • • • • • • • Gastrointestinal problems Helicobacter pylori infection Immune response induction Inflammatory bowel disease Irritable bowel syndrome Malignant colonic disease Pouchitis Rheumatoid arthritis Ulcerative colitis Upper respiratory tract infection Urinary tract health Urogenital tract infection Proven health benefits of probiotics have been used to address prevention and treatment of acute rotavirus diarrhoea and gastroenteritis, antibiotic-associated intestine side-effects and diarrhoea, food allergies and atopic eczema, Clostridium difficile infections, vaginitis (Candida and bacterial vaginosis) and traveler’s diarrhoea. Promising results have been seen in the treatment of Crohn’s disease and ulcerative colitis, asthma, cystic fibrosis, dental caries in children, tuberculosis, irritable bowel syndrome, immune-adjuvants for potentiating oral vaccines and Helicobacter pylori infections. Strikingly, as first established by Metchnikoff, most of these conditions involve the GI tract; these have continued to be a primary focus for beneficial consequences for probiotics. The multiple events necessary for microbial colonisation in the GI tract were well established early in the evolution of microbiology. There are essentially four steps: challenge, adherence, colonisation and critical colonisation/resistance. The establishment of flora in the gut-associated lymphoid tissue is complicated and involves not only the microbiota but the acceptance of the tissue and the blocking or adherence. The process is very complex but now well defined and hence, the hallmark of probiotics and targets of diarrhoeal diseases initially. The list of organisms and specific strains used for treating gastrointestinal diseases and diarrhoea include the lactic acid bacteria, bifidibacteria and Lactobacilli but not all strains are created equal. The probiotic benefits of the organisms are site-and strain-specific. Oral diseases for which probiotics have been evaluated • • • • Dental caries Gingivitis Halitosis Oral candidiasis • Oral manifestations of skin and systemic diseases • Periodontal disease • Xerostomia/Burning mouth syndrome Oral diseases managed by probiotics include gingivitis, caries, chronic periodontitis, Candida albicans, bad breath and xerostomia (dry mouth), and more recently VAP. The key is the manipulation of oral-pharyngeal microbiota, recognising the oral cavity is merely one end of the digestive system. Many strains have been used in oral probiotics. At least 10 strains of Lactobacillus species have been evaluated; the most prominent are L. rhamnosus GG, L. casei, L. reuteri and L. salivarius. Bifidobacteria include a slightly shorter list that includes strains such as B. bifidum (for animals); B. longum; B. breve; B. adolescentis; and the most prominent, Bifidibacterium DN-173010. Although each has had varied success, the following have been observed for each; S. mutans inhibition, reduced yeast counts, and reduced levels of caries-causing pathogens. Establishment of probiotic strains in the oral cavity is complicated by the fact that there are both sloughing and non-sloughing or biotic and abiotic surfaces with established plaque biofilm. To replace and/or out-compete resident native oral flora, the probiotic strains must challenge, adhere, colonise and incorporate into the biofilm. The probiotics must reduce the numbers and activity of seleted pathogenic organisms. To accomplish these goals within this complex environment, the right delivery becomes extremely important. Examples include fortified foods (yogurt, cheese, yogurt drinks); lozenges; rinse solutions; and capsule lichids. The important factors are the formulation, the vehicle of delivery and the frequency of administration. Most often, administration is once or twice daily. The formulation has to acid or alkali stable while at the same time palatable, while the vehicle of delivery has to be stable to deliver the right number of organisms/dose, generally 106 to 108 colony-forming units/ml. Given that probiotics are not the only treatment but are used together with flossing, brushing and aseptic mouth rinse, dose timing is critical. It is obviously of limited value if the probiotic is taken just before brushing and aseptic mouth rinse; the most appropriate time is probably before bedtime, after brushing and flossing. Whether consumed in supplement form or probiotic-fortified foods, probiotics must meet serveral criteria in order to be considered effective. 1. Must have good growth characteristics and be ingested in viable form. 2. Must be able to survive the significant changes in pH of the mouth and the stress factors associated with saliva and the established indigenous microbial community. 3. Must be able to colonise the two surfaces of the oral habitat, recognising sloughing and non sloughing or abiotic versus biotic surfaces. 4. Must be proven in clinical trials to benefit human health by one and/or two of the following pathways: • Replacing or out-competing oral pathogens associated with gingivitis, caries and periodontal disease. • Producing an antimicrobial substance that reduces the number of targeted pathogens. 5. Must prove its worth in double-blinded, placebo controlled clinical trials. 6. Must be biofilm compatible. 7. Delivery, formulation and administration must take into account the traditional brushing, flossing and aseptic mouth rinsing. How do probiotics work? The mechanism of action of probiotics in the oral cavity is based upon two distinct but complementary pathways: replacement of the supplemental pathogenic flora enhanced by antibiotic/chemical activity and/or increase or control immune protection, local and/or systemic. Direct replacement or competitive exclusion involves four sequential steps with the ultimate critical colonisation in a complex microbial community, which is most stable. The immunologic modulation is less well characterised, but also involves a cascade of specific cell markers. Finally, it is important to not confuse the terms ‘probiotic’ and ‘prebiotic’. Prebiotic is a term used for food components that pass through the digestive system but are not digested and can help probiotic bacteria flourish in their attachment niche. Most prebiotics are poorly digested types of carbohydrates that are consumed in an average diet. Prebiotics are often discused as symbiotic to probiotics, i.e., the two benefit from each other. Probiotics in Oral Care Translational research is the term used to describe from ‘bench to bedside,’ showing efficacy in humans as well as animal and laboratory studies. Translational research requires clinical evaluation in humans in the form of double-blind clinical trials with adequate controls and large enough patient numbers to define the statistical benefits. The research studies thus far heighten awareness of the potential benefits. A couple of key observations hold throughout. Organisms utilised are site and strain-specific, often originally found in the gastrointestinal flora; these stains must interfere with the oral biofilm or planktonic present organisms. Strains broadly used are associated with dairy products, yogurt and cheese. Oral probiotics and their connection to diseases of the mouth are discussed here, keeping in mind the oral systemic link: 1. Probiotics and oral colonisation. 2. Probiotics in dental caries. 3. Probiotics in periodontal disease. 4. Probiotics in oral candida albicans/yeast infections. 5. Probiotics and imbalanced oral ecosystems (dry mouth, bad breath, burning-mouth syndrome). 6. Probiotics in respiratory diseases, specifically ventilator-associated pneumonia (VAP). 1. PROBIOTICS IN ORAL COLONISATION Permanent colonisation and replacement of oral pathogens has not been attained but continues to be a goal. Yli-Kuutta e al. in 2006 assessed the colonisation of L. rhamnosus GC in the oral cavities of healthy students, after the 14-day trial the occurance of L. rhamnosus GC decreased gradually, indicating that colonisation was transient; these results confirmed the group’s earlier observations. Kand et al. in 2005 used a relatively new strain, Weissella cibaria, to test for co-aggregation with Fusobacterium nucleatum and their co-attachment to epithelial cells. Fusobacterium is an important ‘bridge’ organism that facilitates bacterial colonisation. It is an important feature in defining the 3D structure of biofilms. Studies demonstrated that certain proteins of the bacterial cell wall may play an important role in the adherence of W.cibaria to the epithelial cells. Houkioja et al. tested the colonisation using different commercial probiotics with Lactobacillus and Bifidobacterium strains obtained from the dairy industry. The results suggested competition amongst Fusobacterium nucleatum and other organisms in establishing colonisation and adherent biofilms. It was apparent that probiotic strains could affect the formation of oral biofims and modify resident microflora. 2. PROBIOTICS IN DENTAL CARIES Benefits of probiotics in reducing dental caries have focused on the replacement of pathogens on the abiotic tooth surface and reduction of pathogens in saliva. A number of lactic acid strains have been employed, but until recently, significant long-lasting results have been unattainable. Lactobacillus rhamnosus GG, L. casei and L. reuteri were all associated with a temporary reduction in S. mutans but continued administration appeared necessary to achieve longer term benefit. Bifidobacterium DN-173 010 was the only Bifidobacterium species that has shown oral colonisation: Caglar et al. in 2005 was able to show significant reductions in salivary S. mutans, but this study was limited, a not uncommon observation in the organism evaluation. Ahola et al. found that a combination of L. rhamnosus GG and L. rhamnosus LC 705 inhibited salivary counts of S. mutans and yeast in young adults over a 3-week period. While this was a well-controlled study with statistically valid data, the study design did not address longterm effects of probiotics in reducing S. mutans as a caries-producing indgenous flora. Montalto et al. evaluated 35 healthy volunteers to assess whether the oral administration of Lactobacillus could change the salivary counts of S. mutans compared with placebo. Lactobacillus counts grew over time whereas S. mutans was reduced marginally, which suggested that probiotic usage may require constant surveillance of challenge organisms. 3. PROBIOTICS IN PERIODONTAL DISEASE Whereas S. mutans is supragingival and involves an abiotic surface, periopathogens are subgingival, in deep pockets where oxygen is very limited. Often, gingivitis and periodontitis are discussed together given the potential role of probiotics for both. The hypothesis has been that the bioburden of periodontal and gingival pathogens could be regulated by means of antagonistic interactions. Krasse in 2006 reported a decrease in gum bleeding and reduced gingivitis with the application of L. reuteri and Koll-Klais in 2005 reported that resident Lactobacilli flora inhabited the growth of Porphorymonas gingivalis and Prevotella intermedia, L. casei in optimal concentrations of 108 CFUs/mL was shown to diminish the number of most frequently isolated periopathogens, Bacteroides species, Actinomyces species, S. intermedius and also Candida albicans. 3. PROBIOTICS IN ORAL CANDIDA ALBICANS/YEAST INFECTIONS C. albicans is one of the most unrecognised yet powerful organisms in the microflora of the oral cavity. It is a biomarker for oral flora imbalance. In ventilator associated pneumonia (VAP) studies C. albicans is referred to as the ultimate coaggregate, and like F. nucleatum is a true building block of biofilms and secondary colonisation in the oral ecosystem. In an interesting randomised double-blind placebo controlled study of 294 elderly patients, aged 70 to 100 years, probiotics reduced the prevalence of oral Candida and surprisingly the risk for hypo salivation in the elderly. Additionally, yeast in the immunocompromised or aged patient may pose a growing problem for the intensive care population with subsequently the emergence of fluconazole resistance. In an animal study, Lactobacillus acidophilus and Lactobacillus fermentum were investigated for enhanced clearance of C. albicans in the oral cavity, and the results proved promising. 3. PROBIOTICS IN RESPIRATORY DISEASES, SPECIFICALLY VENTILATOR-ASSOCIATED PNEUMONIA (VAP) The most recent innovative use of probiotics was a double-blind placebo-controlled study comparing the effects of the probiotic Lactobacillus plantarum 200 (Lp 299) to chlorhexidine in oral decontamination of the mechanically ventilated patient. Klarin et al. randomised 50 critically ill patients in the ICU to cleaning of their oral cavities with either 0.1% chlorhexidine solution or oral application of an emulsion of Lp 299 samples 4 times daily. In this pilot study, the oropharyngeal reduction of potential pathogens were indistinguishable between the 2 treatment groups. Although a limited but growing number of evidence-based publications describe the clinical benefit of probiotics, the use of probiotics by the dairy industry means that it is increasingly difficult to purchase yogurts that do not contain ‘probiotic bacteria’ such as L. acidophilus in order to measure its benefit. While defined in terms as ‘medical probiotics’ (microbial preparation for intervention) and ‘other probiotics’ (functional food), probiotics are provided in products in generally one of four categories: 1. Added to beverage or food. 2. Combined with prebiotic. 3. Added to dairy products. 4. As concentrated and dried cells packaged as dietary supplements or therapeutic addition (nondairy products such as powder, capsules, chewing gum, lozenges or gelatin tablets). Frequently Asked Questions What is normal oral flora? Normal flora is a collection of microorganisms (bacteria, fungi, viruses, etc.) that adapt to the human body, exist as normal residents and establish a healthy, dynamic balance between beneficial and harmful microorganisms. Some normal oral microorganisms include: Streptococcus, Neisseria, Veillonella, Staphylococcus, Fusobacterium, Lactobacillus, Bacterioides, Corynebacterium, Actinomyces, and Treponema. Why is oral care important? Proper oral care is important for several reasons. Our bodies require a balanced, nutritious diet to function at optimum levels. Without teeth, chewing food would be a difficult task. Also, when we do not take proper care of our mouth, poor oral health problem such as gingivitis and cavities can result from the buildup of bacteria. Cavities and other preventable infections lead not only to severe pain and possible loss of teeth if left untreated but also to loss of time from work and potentially high treatment costs. Most importantly, poor oral health affects more than just your mouth. Infections in your mouth can lead to infections in other places of your body. Poor dental health has been linked to several systemic health problems including heart disease, strokes, diabetes, pre-term low-birth weight babies and lung disease. To prevent dental caries, gingivitis, periodontal disease and other oral health problems, it is important to visit the dentist and incorporate an oral hygiene regimen into your everyday routine. A complete oral hygiene routine includes brushing, flossing/interdental brushing and specific products such as mouthwash or probiotic lozenges. This regimen will not only keep your mouth healthy, but your body healthy as well. Are oral infections and diseases hereditary? There has been some research that links oral health problems and genetics but the ultimate cause of caries, periodontal disease, and other oral health problems is failure to adequately remove bacterial plaque. What is a probiotic? The joint consultation of the Food and Agricultural Organisation of the United Nations and the World Health Organisation defined probiotics as ‘Live microogranisms which when administered in adequate amounts confer a health benefit on the host.’ In other words, a probiotic is a valuable bacterial strain ordinarily found in certain parts of the body of a healthy person. When a person’s immune system is out of balance, probiotics can be taken to restore the balance. Probiotics use ‘good, healthy’ bacteria to fight the ‘bad, unhealthy’ bacteria in your body. How do probiotics work? Probiotics work to restore the natural balance of the bacteria in your body. Probiotics have several mechanisms of action. For example some probiotics stimulate the immune system and restore antigen concentration. Other probiotics produce nutrients, vitamins and antimicrobial agents. And some probiotics compete with pathogens for nutrients and binding sites. These mechanisms prevent the overgrowth of unflavourable microflora, restore the number of favourable microflora and provide an environment in which beneficial bacteria can flourish. Where can probiotics be obtained? Probiotic bacteria are very similar to the bacteria found in the body of a healthy person. Probiotics can be found prepared in foods and supplements such as yogurt, cheese and milk. In addition, probiotics can be delivered in tablets, capsules and lozenges. What probiotic supplements for oral health are available in the UK? Oraldiet® is an oral probiotic lozenge that contains Lactobacillus reuteri. Each pack contains 30 mint lozenges, is suitable for vegetarians and contains no artificial flavours or preservatives. Dentalshop supplies this product. For more information about Oraldiet® please contact Kirsty by email at [email protected] or call (01677) 424446 Mon - Fri 9am - 5pm. Oraldiet® is available online at www.dentalshop.co.uk for the general public. Who should take oral probiotic lozenges? Everyone who is at risk for plaque accumulation, gum inflammation, cavities, periodontal disease, or any other oral infections should take oral probiotic lozenges. Especially to benefit are adults and children, pregnant patients, osteoporosis patients, diabetic patients, orthodontic patients, patients who smoke, elderly patients and patients suffering from: • Increased plaque • Gingivitis • Sensitivity • High periodontal disease risk • High caries risk • Immunosuppression • Stress • Adverse effects of medications (oral contraceptives, antihistamines, antidepressants, cancer drugs, steroids, and drugs that cause ‘dry mouth’) What else is in Oraldiet® besides L. reuteri? Oraldiet® is a supplement and should not be used as a substitute for daily food intake. Oraldiet® is suitable for vegetarians but not vegans. Nutritional information average analysis per 1 lozenge Energy value...............................3.3kCal (13.8kJ) Proteins..................................... negligible Carbohydrates............................ 0.8g Fats........................................... negligible How should I take Oraldiet®? Adults and children over 12 years: slowly dissolve one lozenge in your mouth after brushing your teeth and after meals when brushing is not immediately possible. Do not brush your teeth or rinse after taking Oraldiet® as this can reduce valuable oral health benefits of the probiotics. Can Oraldiet® replace brushing and flossing? No. It should only be used with daily brushing and flossing. After brushing and flossing take one lozenge. Oraldiet serves to complete the oral hygiene routine. Brushing, flossing and using supplements ensures optimum oral hygiene, and ultimately a healthy body overall. What are the advantages of taking Oraldiet®? • Inhibits bacterial growth • Reduces plaque accumulation • Reduces gum bleeding and swelling • No soft tissue irritation • No stain • Pleasant taste • Natural, human origin • Safe for children and everyone • Easy to use • Can be added to oral hygiene routine and used with other medications • Supported by clinical research How does Oraldiet® work? A group of microbiologists and dentists have identified a specific bacteria called L. reuteri Prodentis which works by binding to the tissue in your mouth and digestive tract. These bacteria produce a substance known as reuterin that inhibits the growth of bad bacteria responsible for poor oral health (bleeding gums, gum disease, bad breath etc). This strain also has anti-inflammatory effects in the oral cavity. Oraldiet® combats bacteria and helps to restore a balanced oral environment. Is Oraldiet® safe for children? Yes. However Oraldiet® is a lozenge and should therefore only be taken when the patient is old enough to take the lozenge without choking. Is Oraldiet® safe for pregnant women? Yes. In fact Oraldiet® is especially recommended for pregnant women who may experience increased risk to oral infection due to increased hormonal activity. Is it safe to use Oraldiet® with other foods, probiotics or medications? Yes. There are no known adverse interactions between Oraldiet® and other foods, medications or supplements. If you would like to start using Oraldiet® and are unsure whether it is right for you, please talk to your dental professional or pharmacist. Are there any side effects when taking Oraldiet® During extensive clinical research, there are no adverse reactions observed. Oraldiet® does not change the taste of food, stain the teeth or irritate gums. Are there any potential allergens in Oraldiet®? There are no known allergens in oral probiotic lozenges. How does Oraldiet® taste? Oraldiet® has a refreshing mint taste. How should Oraldiet® be stored? In a cool dry place, protected from light and heat. Where can I find more information on Oraldiet®? Dentalshop are stockists for Oraldiet®. For more information on this product please email [email protected] or call (01677) 424446 Mon-Fri 9am - 5pm. Oraldiet® product is listed on our retail site for the general public at www.dentalshop.co.uk