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SAFETY ISSUES IN PROBIOTICS USE

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Authors:Dr. Amit Chawla, Dr. Himanshu Arora, Dr. Namrata Singh.
Consultant oral and maxillofacial pathologist, Gurgaon



ABSTRACT:
The term probiotic meaning “for life” is currently used in reference to bacteria associated with beneficial effects for humans and animals. The observation of the positive role played by some selected bacteria is attributed to work of numerous scientists which resulted in important developments and expansion of knowledge pertaining to the field of probiotics. The most commonly used strains belong to the genera Lactobacillus and Bifidobacterium genera that are commonly found in the oral cavity, including carious lesions. Probiotic Lactobacillus and Bifidobacterium strains have been reported to exert potentially beneficial effects for the mouth. However the safety aspects of probiotics need to be considered and possible adverse effects should continuously be evaluated. Hence a better understanding of the potential mechanisms whereby probiotic organisms might cause adverse effects will help to develop effective ways that predict which strains might not be suitable for use in probiotic products. More knowledge in this regard will also improve guidelines for the use of specific products and will aid in sorting out clinical conditions where probiotic use should be closely monitored.

INTRODUCTION:
The increasing costs of health care and widespread use of antibiotics are driving factors for research and development in the area of functional foods. Although the concept of functional foods was introduced long ago by Hippocrates and his motto ''Let food be your medicine'', more recently scientific community has started to support the hypothesis that diet may play an important role in modulation of important physiological functions in the body.

Among a number of functional compounds recognized so far, biological components from fermented foods and probiotics or the “live microorganisms”, like Lactobacillus and Bifidobacterium species are most notable due to their long tradition of safe use, and established beneficial effects. FAO/WHO (Food and Agricultural organization/World Health Organization) 2002 defines probiotics as “live microorganisms that when administered in adequate amounts confer a health benefit on the host”.1

The applica­tion of 'health-promoting' bacteria for therapeutic purposes is now one of the strongest emerging fields in medicine as well as dentistry Although the use of such probiotics specifically to improve oral health is still in its early stages, oral healthcare workers are probably con­fronted with dietary probiotics on a daily basis. The widespread oral intake of probiotics in the form of preventive and therapeutic products for gastrointestinal health makes these products of considerable interest for oral healthcare workers. These products which usually contain various bacteria such as streptococci, lactobacilli or bifidobacteria can present an oral health risk.2

The review presented here outlines probiotics and their use as a preventive and therapeutic approach in oral health and the potential risks associated with their consumption.

DIFFERENT PROBIOTIC STRAINS:
The majority of probiotics are bacteria with the species of lactobacillus and bifidobacterium being the most common type. Others include yeast and moulds species. Following is the list of micro-organisms currently used as probiotics: 3

1. Lactobacillus species
  • L. acidophilus
  • L. casei
  • L. rhamnosus
2. Bifidobacterium species
  • B. bifidum
  • B. breve
  • B. longum
3. Streptococcus species
  • S. Lactis
  • S. cremoris
  • S. diacetylactis
4. Escherichia coli
5. Fusobacterium species
6. Enterococcus species
  • E. fecalis
  • E. faecium
7. Yeasts and Moulds

CONTRIBUTION OF PROBIOTICS TO ORAL HEALTH:
Given the widespread emergence of bacterial resistance to antibiotics, the concept of probiotic therapy has been considered for application in oral health. Dental caries, periodontal disease and halitosis are among the oral disorders that have been targeted.

| The most commonly used strains belong to the genera Lactobacillus and Bifidobacterium genera that are commonly found in the oral cavity. Probiotics currently have been tried against dental caries, periodontal disease, halitosis, oral candidiasis and oro-pharyngeal infections. Although, to date, the number of studies that have been conducted are limited, the results are encouraging and predict major advances in this field. Different treatment strategies are currently under development.2

To have a beneficial effect in limiting or preventing dental caries, a probiotic must be able to adhere to dental surfaces and integrate into the bacterial communities making up the dental biofilm. The advantage of incorporating probiotics into dairy products lies in their capacity to neutralize acidic conditions. For example, it has already been reported that cheese prevents demineralization of the enamel and promotes its remineralization.4

Probiotics lower the pH so that the plaque bacteria cannot form dental plaque and calculus that causes periodontal disease. They make an excellent maintenance product because they produce anti-oxidants. Antioxidants prevent plaque formation by neutralizing the free electrons that are needed for the mineral formation. Probiotics are able to breakdown putrescence odors by fixation on the toxic gases (volatile sulphur compounds) and changing them to gases needed for metabolism.5

Sookkhee and colleagues in the year 2001 isolated 3,790 strains of lactic acid bacteria from 130 individuals and found that the isolates identified as Lactobacillus paracasei ssp. paracasei and L. rhamnosus had a high capacity to antagonize important oral pathogens, including Streptococcus mutans and Porphyromonas gingivalis.4

Probiotic bacteria, such as Lactobacillus rhamnosus may modify the microbial balance of the host by reducing the overgrowth of pathogens, such as Candida. Certain strains of lactobacilli can adhere to the mucosal epithelium, and may thereby compete for adhesion sites with Candida. In addition, Lactobacillus species produce different metabolites, such as hydrogen peroxide and antifungal cyclic peptides, which inhibit the in vitro growth of Candida. In mice inoculated orally with Candida, lactobacilli have shortened the duration of oral Candidal colonization , possibly by inducing the production of IL (interleukin)-4 and IFN (interferon)-ϒ in lymph nodes and nitric oxide (NO) in the saliva.6

Halitosis, the oral malodor, is a condition normally ascribed to disturbed commensal micro flora equilibrium. It has recently been positively affected by regular administration of probiotics. Kang et al (2006) have shown a definite inhibitory effect on the production of volatile sulfur compounds (VSC) by F. nucleatum after ingestion of Weissella cibaria both in vitro and in vivo.7

Streptococcus salivarius, also a possible candidate for an oral probiotic, has demonstrated inhibitory effect on VSC by competing for colonization sites with species causing an increase in levels of VSC (Burton et al, 2005, 2006a,b). Burton et al (2006a,b) further reported that S. salivarius strain K12 produced two lantibiotic bacteriocins, compounds that are inhibitory to strains of several species of gram-positive bacteria implicated in halitosis.7

SAFETY ISSUES IN PROBIOTIC USE:
Safety is the state of being certain that adverse effects will not be caused by an agent under defined conditions. The reciprocal of safety is risk. The issue of safety for any product is arguably paramount during pregnancy and in newborn babies.8

Probiotic species such as Lactobacillus acidophilus have been safely used for more than 70 years. However the safety aspects have always to be considered and possible adverse effects should continuously be evaluated. Hence a better understanding of the potential mechanisms whereby probiotic organisms might cause adverse effects will help to develop effective ways that predict which strains might not be suitable for use in probiotic products. More knowledge in this regard will also improve guidelines for the use of specific products and will aid in sorting out clinical conditions where probiotic use should be closely monitored.
They may be responsible for four types of side-effects: 8
  • Systemic infections
  • Metabolic and enzymatic effects
  • Immunological effects

Systemic infections:
Rare cases of local or systemic infections including septicaemia and endocarditis due to lactobacilli, bifidobacteria or other lactic bacteria have been reported but the numbers are very low in comparison with other bacteremia cases (incidence of enterococci 5-15%, lactobacilli 0.1%, leuconostocs < 0.01%). Most LAB (lactobacillus) strains linked to clinical cases belong to the species Enterococcus faecium and E. faecalis but a few belong to L. rhamnosus, L. casei or L. paracasei, and L. plantarum. Some cases have also showed other lactobacilli, such as Lactobacillus acidophilus, Lactobacillus jensenii and Lactobacillus paracasei and with Leuconostocs.9

Metabolic and enzymatic effects:

A study per­formed in healthy individuals with a terminal ileostomy demonstrated that L. acidophilus and Bifidobacterium spp. ingested with fermented dairy products could transform conjugated primary bile salts into non-toxic secondary bile salts in the small bowel. This study demonstrates the potential risk of excessive deconjugation or dehydroxylation of bile salts in the small bowel by probiotics.10

Immunological effects:

When administered parenterally, bacterial cell wall components such as peptidoglycans from different gram-positive bacteria, including lactobacilli, can induce side-effects such as fever, arthritis, cardioangitis, hepatobiliary lesions or autoimmune diseases. These side-effects are mediated by cytokines, and it is now well demon­strated that cytokine secretion is elicited by some probiotics.9

Thus, studies that use induction of inflammation as criteria for safety assessment must carefully determine the inflammatory or anti-inflammatory factors that are induced and the end result of the process, with respect to what the probiotic is designed to do for the host. In some cases, the aim will be to enhance immunity to counter cancer or infection, whereas in other cases the aim could be to suppress the inflammatory processes.8

The key to the future of probiotics will be based on the estab­lishment of a consensus on product regulation, including enforcement of guidelines and standards, appropriate clin­ical studies that focus on strengths and limitations of pro­ducts by comparing one probiotic product against another or against standard medical condition and also uncover the mechanisms of action of new strains.

CONCLUSION:
It is clear that the use of probiotics is an interesting emerging area of research in the field of general and oral healthcare. Based on the currently available data, it is apparent that dietary probiotics do not confer a major risk for oral health. No negative effects of probiotic use on oral health have been reported to date. This can probably be attributed to the only temporary oral colonization and the vehicle (milk, yoghurt) in which most of the probiotics are consumed. However, great care is still warranted as repeated daily use of probiotic products over a long period of time will support an increased level of lactic acid bacteria in the oral cavity.

The oral cavity with its diversity of microbial species harbors strains also distinguished as probiotics as such. In this regard further studies identifying resident probiotics of the mouth, understanding the mechanisms of their colonization, and the eventual effect on the oral environment are needed. Studies of the probiotic effect on the balance of the oral ecosystem would also be needed. Of particular interest might be studies on the combined effect of different probiotics applied simultaneously, thus testing the possible addit­ive, cumulative, or competitive modes of action in the oral environment.

BIBLIOGRAPHY:

  1. Vajiljevic T, Shah NP. Probiotics- From Mechnikoff to bioactives. International Diary Journal 2008 July;18(7):714-28.
  2. Teughels W, Essche MV, Sliepen I, Quirynen M. Probiotics and oral healthcare. Periodontology 2000 2008 Oct;48(1):111-47.
  3. Anuradha S, Rajeshwari K. Probiotics in health and disease. Journal of Indian Academy of Clinical Medicine 2005 jan-mar;6(1):67-72.
  4. Bonifait L, Chandad F, Grenier D. Probiotics for oral health: Myth or reality? JCDA 2009 oct;75(8):585-90.
  5. Stomatova I, Meurman JH. Probiotics and periodontal disease. Periodontology 2000 2009;51:141-51.
  6. Hatakka K, Ahola AJ, Knuuttila Y, Richardson M, Poussa T, Meurman JH et al. Probiotics reduce the prevalence of oral candida in elderly – A randomized controlled trial. J Dent Res 2007;86(2):125-30.
  7. Meurman JH, Stomatova I. Probiotics: Contributions to oral health. Oral Diseases 2007 Sept;13(5):443-51.
  8. Reid G. Safe and efficacious probiotics: what are they? Trends in Microbiology 2006;14():348-52.
  9. Salminem S, Wright AV, Morelli L, Marteau P, Brassart D, DeVos WM et al. Demonstration of safety of probiotics – A review. Int J Food Microbiol. 1998;44:93-106.
  10. Marteau P, Gerhardt MF, Myara A, Bouvier E, Trivin F, Rambaud JC. Bifidobacteria and lactobacilli ingested in fermented dairy products can metabolize bile salts in the human small intestine. Microbiol Ecol Health Dis 1995;8:151-57.

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