Probiotics and Prebiotics

• Probiotics may be defined as a preparation of or a product containing viable, defined microorganisms in sufficient numbers, which alter the microflora (by implantation or colonisation) in a compartment of the host. By this effect they exert beneficial health effects on the host.¹
• Prebiotics, in contrast, can be defined as non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria.¹
• A symbiotic contains pre- and probiotics in the same preparation.

Probiotics are arousing a great deal of interest as agents potentially useful for prophylaxis or treatment of a range of gastrointestinal and other illnesses. Many commercially available products are classed as foodstuffs, meaning that claims may be made for their efficacy which need not be as rigorously tested as for a medicine. They have biologically plausible modes of potential action as displacers of pathogens, immunomodulators or local antimicrobial agent secretors. It remains to be seen whether the concept of 'friendly bacteria' is just an 'adman's dream' or a useful biotherapeutic concept. However, initial scientific investigation into the use of probiotic preparations indicates some evidence of usefulness and a definite impetus to continue research into their effects.²

Although this article considers probiotics en-masse it must be remembered that there are a wide range of bacterial strains and preparations in use, and that evidence concerning one particular type cannot necessarily be extrapolated to the class of probiotics as a whole. An increasing body of evidence suggests that probiotics are a useful therapeutic option, particularly in the field of gastro-intestinal disorders.³

Gastrointestinal Disorders

• Prophylaxis of antibiotic-associated diarrhoea Studies with lactobacillus and saccharomyces sp. have shown evidence of benefit, with a reduction in the incidence of diarrhoea from 23 to 13% (NNT~10).⁴ The wide range of antibiotics and organisms used in the various trials and meta-analyses means that definitive conclusions about optimal organisms and strategies are difficult to draw.⁵ A recent comprehensive review failed to demonstrate that the use of probiotics in the prevention of antibiotic-associated diarrhoea in children stood up to intention-to-treat analysis. The review recommended further studies, particularly of those probiotics with the most promising evidence (i.e. Lactobacillus GG, L. sporogens and S. boulardii).⁶ There is as yet no convincing evidence that probiotics can be used to treat antibiotic-associated diarrhoea once it is established.⁷ Trials of probiotic agents in preventing recurrence of Clostridium difficile-associated diarrhoea have shown no clinically significant effects.⁵
• Treatment of acute infectious diarrhoea Meta-analyses have shown that probiotic use may reduce the duration of acute diarrhoea in children by up to 1 day.⁵ The usefulness and cost/benefit analysis of this effect is uncertain. A Cochrane systematic review concludes that probiotics may be a useful adjunct to rehydration therapy in acute infectious diarrhoea in adults and children, but that further investigation is needed to decide on useful bacterial strains and regimens.⁸
• Prevention of traveller's diarrhoea There is no convincing evidence of efficacy for probiotics in this arena.⁵
• Treatment/prophylaxis of inflammatory bowel disease Comparative RCTs into the effect of non-pathogenic E. Coli strains and conventional medical therapies in ulcerative colitis have shown no significant difference in relapse rates in several trials.⁵ However, relapse rates were relatively high in both groups in some trials. Initial studies in Crohn's disease patients in remission showed lower relapse rates with probiotics than mesalazine, but further trials have cast doubt on this finding.^5,9 Double-blinded trials in active Crohn's have shown no benefit in probiotics compared to placebo.⁵
• Pouchitis in patients who have undergone surgical resection This is thought to be mediated by pathogenic bacterial overgrowth and initial good-quality trials with probiotic VSL#3 (4 Lactobacillus strains, 3 Bifidobacterium strains and Strep. salivarius (thermophilus)) have shown promising results. It appears to be much more active than placebo in maintaining remission and in preventing a first attack after surgery.^5,10 It is unclear, as yet, whether active pouchitis will respond to probiotics.
• Irritable bowel syndrome There are no systematic reviews. Some trials have shown benefit and others been more equivocal.⁵ Recent studies suggest a role in immune function, motility, and improving the intraluminal milieu.¹¹
• Eradication of H. Pylori Small trials have given mixed results when given with triple therapy in terms of eradication rates. Any evidence of benefit has been in unblinded trials, and a recent study in which probiotic enriched food was given to children did not show any evidence of an adjunctive effect on H. Pylori eradication.^5,12 One trial showed that patients given probiotics were less likely to develop adverse effects related to the triple therapy.¹³

Atopic diseases

The 'hygiene hypothesis' holds that under-exposure to a wide range of bacteria in childhood causes immune dysfunction and increases the risk of atopic illness. There is a school of thought that those who suffer atopic illness have altered gut flora. Probiotics may therefore be a useful prophylactic or active therapy for atopic illness.

• Prevention of atopy A double-blinded trial of Lactobacillus rhamnosus GG compared to placebo, given to expectant mothers with a family history of atopic illness, showed significantly reduced rates of the relevant diseases in the probiotic group 2 years post-natally,¹⁴
• Treating atopic eczema There is increasing evidence that the introduction of Lactobacillus rhamnosus GG or Bifidobacterium lactis Bb-12 into infant feeding formulae can significantly improves atopic eczema.^14,15
• Treating allergic rhinitis There is some evidence that the use of probiotics can help to alleviate the symptoms of allergic rhinitis, although further studies are required to confirm this.^16,17

Streptococcal sore throat

Super-colonisation using streptococcal strains from patients apparently resistant to streptococcal sore throat, in the throats of those affected by recurrent streptococcal sore throat apparently reduces the incidence of this illness, in several trials. The treatment is experimental and not commercially available at present.¹⁸

Neonatal necrotising enterocolitis (NEC)

A systematic review showed that probiotics might reduce the risk of necrotising enterocolitis in preterm neonates with less than 33 weeks' gestation.. However, further trials are needed in order to assess short-term and long-term safety, dosage, duration, and type.

General benefits

There are many who believe that probiotic preparations given throughout childhood could significantly reduce the incidence of illness in childhood and later life.¹⁹ This will be a difficult hypothesis to prove and will require large well-organised studies to answer the question. Trials focussing on the prevention of infection have shown some evidence of minor benefit for diarrhoea but equivocal findings for respiratory infections.^20,21

A meta-analysis of trials using probiotics for the treatment of gastroenteritis did not report any adverse effects, and probiotics are considered to be relatively safe in most patient groups.^6,22 Reports of adverse effects in trials are of limited value and there is currently much debate about how such effects can be monitored.²³ There have however been reports of severe infections in debilitated or immunocompromised patients, so their use would not be recommended in these groups.^24,25

There is little useful knowledge on interactions between probiotics and other pharmaceutical agents. As experience of their use increases, particularly concomitantly with antibiotics, more information should become available.

As of yet there are no agreed criteria for appropriate bacteria for treatment or prevention of given conditions, size of inoculum, suspension media, accompanying agents/prebiotics, dosing regimens etc. Increased experience through further clinical trials should change this in time.

There are a wide range of commercially available probiotic preparations that make various claims for their beneficial effects. As yet these are largely a marketing proposition rather than verifiable biotherapeutic effects. Use of these products in the healthcare arena should therefore be limited until there is evidence for efficacy in certain clinical scenarios. Medical use of probiotics should be based upon the existing evidence base and be part of a legitimate research or audit program.²⁶