The human colon has been likened to the Dark Continent whose inhabitants are enduring mysteries. For more than a century scientists have mused over the colon flora, unsure of their identity, their nature, or their function. Throughout, there has been a belief that the colon microflora have potential for good or harm. Like it or not they are our closest biological partners and without them our colon would be malnourished, sickly and more exposed to pathogens.
For bacteria to survive in the colon requires a tolerant intestinal immunity. Knowledge of the colon flora is sketchy since the variety of organisms seems bewildering and many species cannot be cultured. Nevertheless, there have been many attempts to alter the colon flora in an effort to promote health and treat disease. Only recently has this become a science.
`Probiotics', a term put forward in 1992, are ‘living microorganisms which upon ingestion in certain numbers, exert health benefits beyond inherent general nutrition’. In order to execute this the organisms must be able to attach to human intestinal cells, colonize the human gut, and resist the effects of intestinal secretions . The most studied organisms in the treatment of human disease are the lactobacilli, notably Lactobacillus GG and Lactobacillus plantarum. These organisms are given orally to treat a number of intestinal diseases and trials are beginning to suggest some benefit.
So far, the most effective use of probiotics is in the treatment of childhood rotavirus infection , where a controlled trial demonstrated that compared to controls, oral Lactobacillus GG treatment shortened the duration of the diarrhoea. In addition, there is early promise in trials of various types of lactobacilli to treat or prevent diarrhoea due to Clostridium difficile , traveller's diarrhoea  and some childhood diarrhoea . There are also encouraging early data supporting their use in inflammatory bowel disease .
Probiotics likely act by altering the gut flora . They might do so by competitive interactions with the indigenous flora, production of antimicrobial metabolites or by modulating the local immune response to enteric bacteria. Oral administration of Lactococcus lactis that was genetically engineered to produce interleukin-10 has been shown to both treat and prevent a mouse model of inflammatory bowel disease (IBD) . Shanahan  points out that such targeted enteral probiotic treatment could provide a superior delivery of interleukin-10 to inflamed intestine then the present expensive, parenteral administration of recombinant interleukin-10 . For such treatment to come to pass, many hurdles remain. Will it work in the human disease? IBD is heterogeneous, so will it be effective in all patients at all stages of the disease? Are there dangers of person to person transmission of these engineered organisms?
With all this activity, it is inevitable that gastroenterologists’ thoughts should turn to the use of probiotics to treat the irritable bowel syndrome (IBS). Two small, randomized controlled trials have produced encouraging results. The first  employed Lactobacillus plantarum (DSM9843) in hip rose tea administered randomly among 60 Rome I-diagnosed IBS patients for 4 weeks. The controls received only the tea. There were eight dropouts, but no observed untoward effects. The 25 treated subjects had a significantly greater reduction in ‘flatulence’ than the controls and a trend towards a greater reduction of abdominal pain. Eighty-four per cent of the treated group acquired Lactobacillus plantarum in the faeces and 34% in rectal biopsies, but no change was demonstrated in the remaining faecal flora. Some improvement was still present a year later, but by then the trial was unblinded and many subjects were taking fermented products.
In this issue of the journal, Niedzielin and his colleagues  report a second study employing Lactobacillus plantarum 299V for 4 weeks randomly among 40 IBS patients diagnosed by the Manning criteria. All the treated patients had resolution of their pain over 2 weeks compared with 11/20 controls. A secondary measure combining pain, stool frequency and consistency also showed improvement.
These results are encouraging, but we have been there before. Treatments that show initial great promise for the treatment of IBS are often left by the wayside when subjected to careful scrutiny. Much larger double blind, randomized, placebo-controlled trials are required, and they must employ a primary outcome measure and ensure that all participants have IBS. The enthusiasm of the participants may inadvertently affect the outcome of small studies such as these, and while the patients may be unaware of their individual treatments, we need strict assurance that the investigators are blinded as well. A third-party observer who is oblivious to the treatment should collect and collate the data.
The lack of a plausible hypothesis is a handicap. It is intuitive to imagine that interactions between the enteric flora and the host may profoundly affect gut function, but we have very little idea what these interactions might be. It is true that IBS patients often remember that their chronic symptoms began with an acute enteritis [10,11], and Collins  has implicated activated inflammatory mediators as responsible for motility disturbances. Might alteration of the colon flora displace organisms responsible for maintaining these changes? Notwithstanding our ignorance, if we are daunted by the lack of a coherent hypothesis, research and treatment trials in IBS will cease. The current enthusiasm for drugs affecting serotonin metabolism or the employment of psychological treatments rests on equally shaky hypotheses.
The possibilities of probiotic treatment are limitless. Not only are there many species of lactobacilli to test, but there are many other organisms in the ‘Dark Continent', perhaps some yet to be discovered. Moreover, it may be possible to beneficently manipulate the colon flora through alterations in the diet, for example through the use of fermented dairy products or grains.
Meanwhile, clinicians should use restraint, and not rush to treat their IBS patients with probiotics. There is much to learn about the colon microflora and its potential for good and bad interactions with the host colon. Moreover, the IBS is equally enigmatic, and via a strong placebo response IBS patients are much subject to the blandishment of new treatments. Until their safety is guaranteed, and their efficacy is unequivocally demonstrated by properly conducted and sufficiently powered trials, probiotics should remain in the experimental arena. They cannot now be claimed effective in IBS. Time and further study may reveal yet another promise unfulfilled.
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