The term 'Probiotics' means 'for life' and is derived from the ancient Greek language. It was first used by Lilly and Stillwell in 1965, to describe substances secreted by one microorganism which stimulates the growth of another; and, thus was contrasted with the term 'Antibiotic'. The unfortunate development of antibiotic resistance seems to be an emerging global challenge that Probiotics seems to offer innovative tools to combat. With the evolution of nutritional science, research is now being directed towards improving the understanding of specific physiologic effects of the diet, beyond its nutritional effect. Hence, Probiotics is a subject of intense and widespread research. Probiotics are described as live micro-organisms which, when administered in adequate numbers, confer a health benefit on the host. There are a few different terms that are used when discussing probiotics: "Prebiotic - (Greek - before life) a substance (usually an oligosaccharide) that cannot be digested but does promote the growth of beneficial bacteria or probiotics. "Probiotic - (for life) a substance that contains microorganisms or bacteria that are beneficial to the host organism. "Symbiotic - (plus life) a substance containing both a prebiotic and probiotic. Traditionally used for digestive health, probiotics are finding a new niche in the dentist's office. The first probiotic species to be introduced into research was Lactobacillus acidophilus (Hull et al 1984) and Bifidobacteriu-mbifidum (Holcombh et al.,1991). To be able to exhibit probiotic effects in the mouth, a bacterium must exhibit the following properties: 1.Should not produce disease or predispose the host to other disease states by disrupting the ecosystem. 2.Should adhere to oral surfaces and become a part of the dental biofilm. 3.Should possess a high degree of genetic stability. A walk through history The 20th century Russian scientist and Nobel Laureate ElieMetchinkoff suggested that it would be possible to modify the gut flora and to replace harmful microbes with useful ones. Ukrainian-born Biologist and Nobel Laureate working at the Pasteur Institute in Paris, discovered lactobacillus bulgaricus in 1907.In 1920, Rettger demonstrated that Metchnikoff's "Bulgarian Bacillus", later called ''Lactobacillus delbrueckii subsp. bulgaricus'' could not live in the human intestine, and the 'fermented food phenomena' petered out. Metchnikoff's theory spelt controversy (at this stage).Later in 1953, trials were carried out by the medical fraternity using this organism, and encouraging results were obtained especially in the relief of chronic constipation.The concept of probiotics was thus re-born and a new field of microbiology opened. The Modus operandi I.The concept of Antagonism. Probiotics are based on the concept of "Bacterial Interference", whereby one microorganism can prevent and/or delay the growth and colonization of another member of the same or different ecosystem. Two approaches by which bacterial interference is being considered as a means of enhancing colonization resistance in plaque to prevent periodontal diseases are: i. Pre-emptive colonization: Ecological niches within plaque are bombarded with harmless or potentially beneficial organisms (aggregation) before the undesirable strains have an opportunity to colonize & establish itself. Among probiotic strains, L. rhamnosus exhibits the highest value of adhesion, comparable to those of the early tooth colonizer: S. sanguinis. ii. Competitive Displacement: A competitive strain would displace a pre-existing organism from an adhesion site. It is not dependent on treatment with the 'effector' strain at or before colonization by the undesired organism. There is data to suggest that this happens due to a molecule expressed by Gram-positive bacteriae, called lipoteichoic acid (LTA). LTA, which looks structurally very similar to a molecule expressed by pathogenic bacteria, is able to out-run and hence bind tighter to a receptor on the adhesion site, thereby blocking the inflammation pathway. II. Inhibition of pathogen growth. i.Probiotics like Lactic acid bacteria produce different antimicrobial comp-onents such as organic acids, hydrogen peroxide, carbon peroxide, diacetyl, low molecular weight antimicrobial substa-nces, bacteriocins, and adhesion inhibi-tors. ii. Compete for nutrients and growth factors. iii.Chemical barrier lowers salivary Ph in-turn creating acidic conditions unfav-ourable for pathogenic growth. III.Immunomodulation Probiotics modulate the Innate and Adaptive immune response of the patient. Principles of Innate Immune Response (IIR) and Adaptive Immune Response (AIR). 1.IIR initiates AIR and eliminates infection. 2. There is delay of 4-5 days before initiation of initial AIR swings into action, in the mean time IIR plays its role in controlling infections. 3. Microbes express microbial assoc-iated molecular patterns (MAMPs) which induce the secretion of cytokines and chemokines which trigger inflamm-ation. Toll like Receptors (TLRs) are one of the most extensively studied, most important signaling molecules in an Innate Immune Response. In humans, there are at least 10 TLRs that are capable of recognizing unique molecules expressed exclusively by microbes. Examples of microbial-associated molecular patterns (MAMPs) include: lipopolysaccharides (LPS), flagellin, and single stranded RNA (ssRNA) which stimulate immune cells to become highly inflammatory. Bacterial lipopolysaccharides activate TLR-4 leading to release of IL-8 (neutrophil chemotactic factor) and TNF-? (induces apoptic cell death and regulator of immune cells) which initiates a cascade of an inflammatory response. In response to bacterial lipoteichoic acid (Gram positive strains) recognize TLR-2 which induces release of IL-10 (Anti-inflammatory cytokine) and T-regulatory cells. Adaptive immune response. Toll-like receptor signaling triggers dendritic cell maturation, which primes naive T-lymphocytes towards specific T-helper cells, further causes induction of T regulatory cells that suppress certain immune responses that may be critical to immune regulation. A few years ago, it was discovered that a MAMPs located on the Gram-negative bacteria Bacteroidesfragilis called polysac-charide A (PSA) can also stimulate TLR-2.Bacteroides alone make up 30% of gut bacterial flora. B fragilis actively blocks inflammatory Th17 development in the gut by expressing PSA. Human ?defensin (hBD) are a family of mammalian defensins. They are antimicrobial peptides implicated in the resistance of epithelial surfaces to microbial colonization. Probiotic effect on human ?defensin (hBD) secretion by oral epithelial cells may also serve as an evaluation criterion for immune-stimulatory properties of these species. Human ?defensins have been identified in the oral cavity with broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi and enveloped viruses. In the oral cavity hBD-2 is expressed in oral epithelium in normal un-inflamed gingival tissue presumably because of the high level of exposure to commensal microorganisms. Clinical Benefits: Probiotics and dental caries: "Probiotics", as used here, means that mechanisms are employed to selectively remove only the (odonto) pathogen while leaving the remainder of the oral ecosystem intact. 1. Replacement therapy options entails the application of a genetically engineered "effector strain" of S. mutans that will replace the cariogenic or "wild strain" to prevent or arrest caries and to promote optimal remineralization of tooth surfaces that have been demineralized but that have not become cavitated. S. mutans strain BCS3-L1 is a genetically modified effector strain designed for use in replacement therapy to prevent dental caries. Recombinant DNA technology was used to delete the gene encoding lactate dehydrogenase in BCS3-L1 making it unable to produce lactic acid. This effector strain was also designed to produce elevated amounts of a novel peptide antibiotic called mutacin 1140 that gives it a strong selective advantage over most other strains of S. mutans. 2. Genetic modified plaque strept- ococci create organisms that produce ammonia from urea and arginine.
