Probiotics and prebiotics for health

The complexity of modern medicine and the risks it carries while using has made people to think of better alternatives like prevention of diseases, which are as natural and environmentally friendly. A complex population of micro-organisms inhabits the gastrointestinal tract throughout its length. The colon is the main site of colonization. Recent molecular studies have confirmed the concept of microbial diversity within the gut. This gut microbiota plays a very significant role in maintaining the dividing line between human health and diseases. The main function of this microbiota is to check colonization by potentially pathogenic micro-organisms, by competing pathogens for ecological niches and metabolic substrates. It meets about 50 per cent of the daily energy requirements of the colonocytes by the fermentation of carbohydrates to organic acids. The microbiota acts as an important modulator of the immune system, not only refining the infant immune system but also helping as non-inflammatory immune stimulator throughout life. This microbiota is not infallible and can be overcome by pathogens leading to gastrointestinal infections. This conception has lead to the development and commercialization of probiotics and prebiotics as a microbiota management tool, shifting the balance back to the beneficial flora.

Probiotics
The word ‘probiotic’ means ‘for life’ and is derived from the Latin ‘pro’, which means ‘for’, and the Greek ‘biotikos’, which means ‘living’. A probiotic has been defined as ‘a live microbial food ingredient that is beneficial to health’. Most of the probiotics belong to the genera lactobacilli and bifido-bacteria. These genera have a considerable safety record, as they are being used in fermented food industry for years. A number of criteria are used to select for probiotic strains. An effective probiotic must be non-pathogenic and non-toxic and exert a beneficial effect on the host. Moreover, they should be capable of surviving passage through the GI tract, particularly the harsh environmental conditions in the human stomach and small intestine (e.g. gastric acid, bile acid and digestive enzymes), and compete along with a highly-diverse and competitive environment presented by the human gut microflora. They should adhere to the intestinal epithelial cell lining (as it may increase persistence in the gut), must produce antimicrobial substances towards pathogens, remain viable during storage and use, have good sensory properties and should be isolated from the same species as its intended use. A perfect digestive system is rare, and most people experience heartburns, bloating, burping and gas from time to time. A positive effect of probiotics is that they scavenge indigestible molecules throughout the GIT. Probiotics produce enzymes that promote breakdown and food digestion. Thereby, reduce the events of bloating, gas and putrefaction and improves the utilization of nutrients and much more.

Probiotics for diarrhoea
A wide range of probiotic strains has been evaluated for their anti-diarrhoeal capabilities, with varying degrees of outcomes. In acute infantile diarrhoea, often due to infection with rotavirus, Lactobacillus rhamnosus GG has repeatedly shown the duration of diarrhoea by 50 per cent. Diarrhoea occurs in about 20 per cent of the patients on antibiotics. The antibiotics might directly affect the indigenous gut microbiota by compromising the colonization resistance and favouring the growth of pathogenic microbes, for example clostridium difficile and klebsiella oxytoca. Certain probiotic strains are observed to reduce the incidence and duration of diarrhoea. Bifidobacterium longum, L. bacillus and L. rhamnosus GG has shown decreased incidence of erythromycin-induced diarrhea, whereas L. acidophilus reduced the incidence of clindamycin and ampicillin-induced diarrhea.

Oksanen et al in 1990 investigated the ability of L. rhamnosus GG to prevent diarrhea in 820 volunteers travelling in turkey. In only one of the holiday destinations, there was a significant reduction in the incidence of diarrhoea among travellers taking probiotics. This study highlights the mechanistic problems associated with prophylactic trials on the effect of probiotics against traveller’s diarrhoea. Not only because the disease is caused by diverse, ever-changing flora of microbial pathogens, but also due to the involvement of pathogenic E. coli, Salmonella, Camphylobacter and Shigella strains as well as viruses. It is unlikely that a single probiotic strain will inhibit such a broad spectrum of pathogens.

Probiotics in inflammatory bowel disease
A group of specific nonpathogenic bacteria strains are functionally and genetically defined by their ability to reduce inflammation in the intestine. Although probiotics also seem to have broad beneficial effects in humans, both as a food and as a therapeutic agent, there are specific identified mechanisms in some, but not all, of these bacteria that are important relative to the pathogenesis of inflammatory bowel disease. Recently, studies relative to the mechanism of action of probiotics have identified that these organisms can have a direct effect on epithelial cell function and intestinal health, including enhancing epithelial barrier function, modulating epithelial cytokine secretion into an anti-inflammatory dominant profile, altering mucus production, changing bacterial luminal flora, modifying the innate and systemic immune system, and inducing regulatory T-cell effects. For probiotics to have a therapeutic role in the management of clinical inflammatory bowel disease, their therapeutic mechanism of action must be aligned with the pathogenic mechanism of action of the disease. In this regard, the role of probiotics for the clinical treatment of inflammatory bowel disease is emerging as the mechanisms and pathogenesis is being unravelled. It remains clear that probiotics are able to reduce gastrointestinal inflammation by exerting positive effects on epithelial cell and mucosal immune dysfunction.

Probiotics and their action
A significant question regarding clinical use of probiotics is the mechanism underlying the wide range of actions. The mode of action of probiotics is found to be multi-factorial and varies strain to strain. Probiotics have inhibited the pathogenic strains both in vitro and in vivo through various different mechanisms.  Studies show various distinct cellular and molecular mechanisms for probiotic regulation in IBD therapy. These include blocking pathogenic bacterial effects by producing bactericidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium, regulating immune responses by enhancing the innate immunity and modulating pathogen-induced inflammation via toll-like receptor-regulated signalling pathways, or regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, competing for nutrients, enhancing barrier function, and stimulating protective responses. Probiotics modulate host cell signalling pathways, including Akt, mitogen-activated protein kinases, and nuclear factor-?B to mediate these intestinal epithelial functions. It is hoped that developing a mechanistic understanding of probiotic action will provide the rationale to support the development of new hypothesis-driven studies to define the clinical efficacy in preventive, adjunctive, or alternative treatments for IBD and other disorders. An alternative approach to probiotics for intestinal flora modulation is the use of prebiotics. A prebiotic is ‘a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon. For a food ingredient to be classified as a prebiotic, it must: (a) neither be hydrolysed nor absorbed in the upper part of the GI tract; (b) be a selective substrate for one or a few beneficial bacteria in the colon (e.g. lactobacilli and bifidobacteria); (c) consequently be able to alter the colonic microflora towards a healthier composition.

The premise behind prebiotics is therefore to stimulate certain indigenous bacteria resident in the gut rather than introducing exogenous species, as is the case with probiotics. Ingesting a diet containing non-digestible carbohydrates that are selectively fermented by indigenous beneficial bacteria is the prebiotic principle. Any dietary component that reaches the colon intact is a potential prebiotic. However, most of the interest in the development of prebiotics is aimed at non-digestible oligosaccharides. These oligosaccharides are considered to be the most important prebiotic substrates because they meet all the current criteria for prebiotic classification. Oligosaccharides are sugars consisting of between approximately two and twenty saccharide units, i.e. they are short-chain polysaccharides. Apart from those that occur naturally in fruits and vegetables, and are extractable, others can be commercially produced by the hydrolysis of polysaccharides (e.g. dietary fibres, starch) or through enzymic generation.

Application of probiotics, prebiotics in infants’ health
As prebiotics exploit the use of non-viable dietary components to improve gut health, the range of foods into which they can be added is much wider than that for probiotics, where culture viability needs to be maintained. The prebiotic approach has the advantage that heat stability or exposure to O2 is not an issue and it is concentrated towards stimulation or enhancement of the indigenous probiotic flora. Hence, for practical as well as aesthetic reasons their use in formula feeds currently seems to be more widespread than the use of probiotics. The faecal flora of breast-fed infants is dominated by populations of bifidobacteria, and comprises only about 1 per cent enterobacteria. It is thought that certain bifidogenic factors are present in human breast milk. In contrast, formula-fed infants have a more complex microbiota, with bifidobacteria, bacteroides, clostridia and streptococci all being prevalent Lactulose, a bifidogenic substrate was used as an adjunct to formula feeds in the 1950s. However, today it is not used as a foodstuff because it is not licensed as such, because of its laxation effect at high doses. Two non-digestible oligosaccharides currently used in infant formulas are the fructo-oligosaccharides and galacto-oligosaccharides.

Use of probiotics, prebiotics for colon cancer
Ingestion of viable probiotics or prebiotics is associated with anticarcinogenic effects, one mechanism of which is the detoxification of genotoxins in the gut. This mechanism was shown experimentally in animals with use of the rat colon carcinogen 1,2-dimethylhydrazine and by determining endpoints that range from tumorigenesis to induction of DNA damage. Because of the complexity of cancer initiation, cancer progression, and the exposure of cancer in the gut, many types of interactions may be envisaged. Notably, some of our newer studies showed that short-lived metabolite mixtures isolated from milk that were fermented with strains of Lactobacillus bulgaricus and Streptococcus thermophilus are more effective in deactivating etiologic risk factors of colon carcinogenesis than are cellular components of micro-organisms.

Ingestion of prebiotics results in a different spectrum of fermentation products, including the production of high concentrations of short-chain fatty acids. Gut flora, especially after the ingestion of resistant starch, induces the chemo-preventive enzyme glutathione transferase p in the colon of the rat. Together, these factors lead to a reduced load of genotoxic agents in the gut and to an increased production of agents that deactivate toxic components.  Butyrate is one such protective agent and is associated with lowering cancer risk. It was recently shown that buytrate may inhibit the genotoxic activity of nitrosamides and hydrogen peroxide in human colon cells. In humans, the ingestion of probiotics leads to the excretion of urine with low concentrations of components that are genotoxic in human colon cells and high concentrations of components that induce oxidized DNA bases.

Synbiotic approach
A synbiotic is a supplement that contains both a prebiotic and a probiotic that work together to improve the “friendly flora” of the human intestine. A synbiotic product should be considered a “functional food” rather than some obscure chemistry formulation. A further possibility in microflora management is the use of synbiotics.  A Synbiotic affects the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract, by selectively stimulating the growth and/or activating the metabolism of one or a limited number of health-promoting bacteria, and thus improving host welfare. Synbiotics aim to enhance the survival and activity of proven probiotics in vivo as well as stimulating indigenous bifidobacteria.

Synbiotic intervention has shown significant changes in fecal flora: Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased. The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients. Genotoxicity assays of colonic biopsy samples indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period. Synbiotic consumption prevented an increased secretion of interleukin-2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon ? in the cancer patients. Synbiotic products have the potential for enhanced health promotion over probiotics or prebiotics but require further deeper investigation in human feeding.

Conclusion
The intestinal microbiota forms a diverse and complex ecosystem. However, there is much variability in bacterial numbers and populations between the stomach, small intestine and colon. In comparison with other regions of the GI tract, the human colon is an extremely-densely-populated microbial ecosystem. The large gut microflora is acquired at birth. Initially, facultatively-anaerobic strains such as Escherichia coli dominate. Later, differences exist in the species composition that develops, and is largely governed by the type of diet. The faecal flora of breast-fed infants is dominated by populations of bifidobacteria, whereas in formula-fed infants a more complex microbiota with bifidobacteria, bacteroides, clostridia and streptococci are being prevalent. After weaning, a pattern that resembles the adult flora becomes established. This critical stage of development is likely to affect health status in later life. Microflora modulation can occur through diets that contain probiotics and/or prebiotics, and are applicable to use in infant feeds.

The interest in gut flora modulation has generated data whereby human well-being can be enhanced and the risk of the disease onset reduced. New advances that use the symbiotic effect, target distal colonic activity and improved functionality, as well as wider range of delivery systems can further wax the range of possibilities.