Probiotics and Prebiotics
BY: Dr. Gareth Parkes MRCP Clinical Research SpR in Gastroenterology, Kings College London.
Probiotics and Prebiotics
The term probiotic, which has been in common use for the last 10 years, is derived from the Latin "for life" and interestingly has a similar meaning to an ancient Assyrian word for yoghurt "Lebeny" which was also their word for 'life'. The WHO & UN Food and Agriculture Organization have defined the term probiotic as "live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host." Over the last few years there has been an explosion of interest in probiotic or friendly bacteria both in the scientific world and in the food industry where probiotics field has been estimated to be worth billions of dollars. How do they work? Which strains are most effective? What can we expect them to achieve and what sort of numbers are required to be beneficial? We do know they can be beneficial not just for patients with digestive problems such as irritable bowel syndrome but could they play a crucial role in allergic conditions in which what we eat is commonly seen as a potential trigger.
Our Commensal Flora
Before scrutinizing the claims and possible benefits of probiotics it is useful to look at our gut's natural flora. The human body contains anywhere between 1012 and 1014 bacteria, the majority of these bacteria colonise the gut, predominantly the colon or large intestine and can make up to 40% of the weight of our stool. This means that bacteria out number our own human cells by an incredible 10 to 1. We know that the gut is rapidly colonized from birth and contains between 400-500 species of bacteria most of which are unculturable by conventional methods. It appears that these bacteria play a number of key roles in our lives. They are crucial to the development of a healthy immune system, play a protective barrier role against invasion of pathogenic strains of bacteria, promote normal contractions of the bowel and are crucial in digestion of certain foods releasing vitamins and nutrients such as short chain fatty acids. Against this background it is easy to see why modulation of the gut's natural flora might be of potential benefit.
Probiotic Preparations
There are now a very large and diverse range of probiotics on the market currently either in the supermarkets, health food shops or available over the internet. There are different delivery systems such as yoghurts, drinks, powders and tablets and they can contain are enormous differences in bacterial numbers from 150 million to 450 billion per daily dose. The earliest recorded probiotic was E. Coli Nissle isolated in a World War I soldier in 1917. Currently most commercial probiotic products contain a variation on three key bacterial species: Lactobacilli, Bifidobacterium and Streptococcus thermophilus. Most trials suggest that in order to have a reasonable effect on the natural gut flora doses of probiotics need to exceed 108 per day (this is either written as .
In contrast to probiotics, prebiotics are complex sugars such as inulin and fructo-oligosaccarides (FOS) which the human gut is unable to breakdown. These sugars which the human body is unable to metabolise act as a food source for the body's commensal probiotics, in particular boosting numbers of Bifidobacteria spp. Synbiotics are preparations containing both a probiotic and a prebiotic in combination in order to try and boost numbers and improve colonisation in the gut.
Mechanism of Action
There are a number of putative mechanisms through which probiotics might exert their influence on the host.
- All bacteria interact with the host immune system via a system of receptors known as 'Toll like receptors' or TLR's. Probiotics have been shown to have profound anti-inflammatory effects on the host immune system through these interactions which can even occur when the bacteria are dead. These anti-inflammatory effects may promote tolerance of potential dietary antigens.
- Anti-bacterial effects through the release of anti-microbial peptides and chemicals
- A direct barrier effect preventing pathogenic strains from adhering and invading the host epithelial layer
- Competing with pathogenic bacteria for nutrients thereby suppressing their proliferation
- Increased mucin production and decreasing the intestinal permeability preventing antigen and bacterial invasion
When should we use probiotics?
There are many claims of benefits of probiotics so below is a summary of the evidence for various conditions:
Allergy
It is estimated that 20-30% of the western world suffers from allergy related diseases such as asthma, eczema and rhinitis, included in these are the 5-6% of young children and 2-4% of healthy adults who suffer from food allergies. There are a number of ways in which the foods we eat can be modified to switch off the allergic pathways in prone individuals and the use of probiotics is one of these. The use of probiotics in atopy fits neatly into the hygiene hypothesis which suggests that the increase in allergic disease in children is because of decreased exposure to bacteria and dirt in our westernized urban lifestyle. We know that the first few months and years of life appear to be crucial in the maturation of the immune system and development of allergic type responses. Modulation of the immune system by introducing anti-inflammatory, anti-allergy bacteria is perhaps the best way we can 'cure' this problem from the outset rather than spending the rest of a patient's life attempting to reduce the allergic response with medication and diet.
The data for the benefits of probiotics in allergic conditions is best demonstrated in eczema or atopic dermatitis. There are a number of good randomised placebo controlled trials of probiotics in infant eczema which show improvement in symptoms over placebo, including one trial that looked at children who developed eczema as a result of cow milk protein allergy (CMPA). 230 of these infants were treated with one of four probiotics for 4 weeks and all groups showed a reduction in dermatitis scores 4 weeks later however one probiotic Lactobacillus GG (LGG) showed the greatest reduction in symptoms in those infants who were skin prick positive for CMPA. Perhaps more excitingly there has also been one study in prevention rather than treatment of eczema by the same group. This trial gave pregnant women, who had strong family histories of atopic dermatitis, Lactobacillus GG for 2-4 weeks pre-natally and then the newborn child for 6 months. They found administration of probiotics halved the incidence of atopic dermatitis at 1 year by half from 46% in the untreated group to 23% in the treated group. This benefit continued through to 4 years were the risk of developing eczema in the group treated with probiotics was 0.57 when compared with those not treated. It is certainly conceivable that further work in this field may produce better more specific bacteria, but more work will be required to understand exactly how these bacteria exert their influence.
Irritable bowel syndrome
After the worried well the next largest market for probiotics is probably sufferers of irritable bowel syndrome or IBS. Although the exact aetiology of IBS remains unclear there is a possible link with food intolerances. One possibility in how diet may work is that foods such as carbohydrates and dairy products might act as a substrate to the bacterial flora, there by suggesting a mechanism by which probiotics may work. Equally the allergic action of dietary antigens may be counterbalanced by the anti-inflammatory effects of probiotics. Finally people with lactose intolerance might well benefit from probiotics therapy strains from the lactobacillus family contain natural lactase activity.
Numerous trials have been undertaken to look at possible benefit with rather mixed results. Many have been hampered by enormous placebo effects, a common feature of many therapeutic trials in IBS, with one trial showing 60% placebo benefit making it almost impossible for the probiotic to achieve a significant improvement.
The best current evidence remains probiotics reduce the symptom of bloating in IBS and that they are unlikely to have a profound impact on bowel frequency or consistency. The sensation of bloating is an interesting one and studies have shown that it can correlate with actual abdominal distension which in turn has been shown to be due to increased gas production in the small bowel. Gas production is likely to be secondary to fermentation of sugars and carbohydrates by bacteria in the small bowel and probiotics probably act by competing with fermenting bacteria for food.
Inflammatory Bowel Disease & Pouchitis
There has been much interest in the use of probiotics in IBD over the last 10 years. A strong case can be made for their use in IBD as microbiological work in both Crohn's disease (CD) and Ulcerative colitis (UC) has shown imbalances in bacterial flora . Both conditions show a reduction in natural probiotics and increased pro-inflammatory strains such as E. coli, Bacteriodes & Clostridium spp. In a condition known as pouchitis there is inflammation of an ileal pouch constructed post-colectomy. Pouchitis responds extremely well to antibiotics and the length of remission can be increased with VSL#3 a commercial cocktail of 8 probiotics given in very high numbers 3x1012 per day (3 trillion) when compared to placebo.
In UC 2 trials of E. coli Nissle showed that it was at least equivalent to standard therapy using mesalazine in maintaining remission over a period of a year however a third study suggested that although Nissle was equivalent to mesalazine therapy neither were particular good at maintaining remission compared to placebo . There is some open label work showing good remission rates when using VSL#3 but at this stage only in small numbers and not placebo controlled. Interestingly there is a small pilot study showing reduction in symptom scores in patients with active CD taking open label prebiotic preparations containing FOS however again a larger study is required.
Discussion
The use of probiotics has undertaken a revolution in the last 10 years which few 'alternative therapies' have ever managed in the past. Their use has come from theoretical claims on the fringes of healthcare to multi-centre randomised placebo controlled trials and meta-analysis. There is no doubt that they will continue to play an ever increasing role in a number of areas of medicine. However if we are ever to maximize the benefits of these friendly bugs we have to understand far more completely their mechanism of action and their complex interaction with the human immune system.
The FAIR connection with King's College London
Dr. Gareth Parkes, the author of the above article, is a researcher at King's College London. FAIR is presently funding a Senior Clinical Research Fellow and a Clerical Research Associate within the Food Allergy and Environmental Health Research Group at King's College London. Read more about the work of the Food Allergy and Environmental Health Research Group.