Prebiotics and Probiotics
Pre-biotic is the name given to chemicals which may increase the growth of healthy bacteria in the gut. Interest in probiotics stemmed from the realisation that the use of probiotics – actual living bacteria – was limited by the body’s immune defences. New bacteria entering the gut, be they healthy or pathogenic, are recognised as ‘outsiders’ and are usually rapidly eliminated. This considerably limits the effectiveness of treatment by probiotic bacteria. It was shown that pre-biotic chemicals such as inulin and fructose-oligosaccharide would increase the numbers of Bifidobacteria in the bowel of healthy volunteers, and it was hoped that the unbalanced microflora seen in conditions such as IBD and IBS, where there are reduced levels of Bifidobacteria and increased numbers of oxygen-loving commensals such as coliforms, Proteus and Klebsiella, might therefore be corrected.
Pre-biotic chemicals, for example inulin, fructose-oligosaccharides or lactulose, all share the same property of passing down the small intestine without being digested, so that they reach the bacteria in the lower bowel unchanged and can be fermented by them., Unfortunately the therapeutic value of these substances has been disappointing. It would appear that although they may increase the numbers of healthy bacteria present in normal volunteers, but that when the bacterial balance is disturbed, in disease states, the bad bacteria get just as much benefit from fermenting the probiotics as do the healthy bacteria. This may mean that there is generally little improvement and that conversely sometimes the condition may even get worse. Despite great initial enthusiasm, therefore, the role of probiotics in IBD remains unproven, although undoubtedly further research in this field will be done.
Probiotics are live microbial food ingredients that alter the enteric microflora and have a beneficial effect on health.
The gut flora consists of over 400 different species and is relatively stable throughout life, but is distinct in different individuals. These bacteria contain many enzymes whose activity is such that metabolic transformations in the bowel may rival the importance of those in the liver. Whilst the effect of this metabolism is generally beneficial producing for example vitamins and nutrients (short chain fatty acids) and breaking down carcinogens, under certain circumstances the flora may cause disease when the numbers of certain pathogenic bacteria such as Clostridium difficile increase.
A number of observations suggest the bowel flora may be important in causing IBD. Gut lesions have been shown to be most frequent in the areas of highest bacterial concentration. If the faecal stream is diverted disease affecting the bowel further down may heal. Furthermore, lesions of Crohn’s disease may be induced by instillations of faecal content to apparently unaffected loops of bowel. The gut mucosa produces antibodies that coat as much as 80-100% of normal bacteria in IBD, but less than 20% in healthy controls. Finally rats and mice, which have been bred lacking certain anti-inflammatory cytokines such as IL-10, will spontaneously develop colitis but only if bacteria are present in the gut.
For these reasons modification of the activity of the gut flora has been investigated as a way of controlling IBD. Antibiotics such as ciprofloxacin and metronidazole may prove very helpful but cannot be used for long periods because of the risk of bacterial resistance developing. As discussed elsewhere the effectiveness of liquid diets may be due to their reducing the metabolic activity of gut bacteria. Probiotics may prove beneficial by displacing other pathogenic bacteria or by promoting healthier metabolic pathways. They have not yet been widely used in IBD because the anti-inflammatory activity seems modest. A strain of Lactobacillus salivarius appears to improve colitis in IL-10 deficient mice. A non-pathogenic strain of E. coli was reported to be as effective as mesalazine in UC. VSL-#3, a cocktail of eight strains of bacteria has been shown to be highly effective in patients with pouchitis.
In the future it seems likely that vigorous attempts will be made to find suitable probiotic organisms for the treatment of IBD. Apart from a search for new strains and more complex mixtures of different bacteria, genetically engineered organisms may be developed, possibly containing anti-inflammatory molecules such as IL-10. However, there is still considerable work to be done before probiotics can be considered as part of the standard treatment of IBD.