What encouraged doctors at the Royal Sussex County Hospital in Brighton to put patients on probiotics was a randomised controlled trial, published in 2007, which found that a yoghurt containing three probiotics cut down the amount of diarrhoea patients suffered as a result of being put on antibiotics to treat the bug C.difficile, which they had picked up in hospital. 
The general public, however, aren’t so cautious. They clearly believe that probiotics are beneficial – around two million Britons now spend an estimated £135 million on buying drinks, yoghurts and capsules containing probiotics. Meanwhile, the medical mainstream continues to regard the gut largely as a form of plumbing to unblock or solidify, to be treated with drugs to damp down inflammation or acid if either seem to too high – and finally to be chopped out if none of that works. What this fails to take into account is the extraordinary complexity of the gut, not least of the ecosystem of the bacteria inhabiting it.
There are more than a thousand species living in our guts, most of which can not be grown in cultures in the lab, and these are intimately involved in the workings of our immune system, as well as helping us extract nutrients and metabolise waste.
A Hidden Sense?
This hidden world was vividly described at a conference three years ago in Dublin by Professor Fergus Shanahan of the Alimentary Pharmabiotic Centre at the University of Cork. He described the constant cross-talk between the bacteria and the “mucosal layer”’ that lines the gut walls, creating a system “which has more cells than the spinal chord and forms the largest metabolic and immune organ in the body with direct connections to the brain.” In fact, Shanahan went on, it behaves like one of the senses. “It has receptors and information flowing in and out that has to be integrated and organised, so it also has memory and learning.”
As with other senses, if it’s not set up properly at the beginning of life and doesn’t get the necessary stimulation, it won’t function so well. “At birth, beneficial bacteria from the mother have to colonise the gut, a process which can be delayed in the case of caesareans,” he said. “Then without the stimulation of some sort of infection, development of the immune response is poor and the chronic inflammation we see in IBS [Irritable Bowel Syndrome] can be the result.” In fact, the result of unbalancing our gut flora could be even more disastrous. Research just published suggests there could be a biological equivalent of global warming going on down there.
Just as our energy consumption is warming up the planet, so the changes in our foods, changes in birth practices, the increasing sterility of our houses and the widespread use of antibiotics all have combined to dramatically alter the make up of our gut bacteria – quite possibly contributing to the recent steep rise in allergies and auto-immune diseases.  But the impact of the activities of our microbial flora isn’t limited to the immune system. The remarkable fact that if you were to add up all the DNA in our bodies, 90% of it would come from the bacteria that inhabits us has huge implications for applying the human genome to health. Take the attempts to predict who will respond well or badly to a drug, based on their DNA. “Drug companies have spent millions trying to tell who’s most likely to have side effects from particular drugs based on variations in their genes,” says Dr Jeremy Nicholson of Imperial College, London. “But just focusing on the human genome is almost certainly doomed to failure unless you take into account the actions of the genes in the gut. The gut is where most drugs are broken down and if you don’t have enough of the right strains of bacteria to do the job, you are likely to have problems.”
What you have here is the paradox of probiotics. On the one hand, mounting evidence of a complex gut ecology with huge implications for health. On the other, no more than a handful of properly conducted trials showing that this bacterial strain given for that condition is better than a placebo. The issues this raises – the trials have not been done because bacteria can’t be patented, so who should pay for them – are best left for another time. Nicholson’s response to this impasse has been to establish a biochemical evidence base so that probiotics, rather than being regarded as some sort of slightly wacky non-drug treatment for conditions that aren’t responding well to pharmaceuticals, will be able to move into the mainstream. In a new study in January 2008, he showed that just giving standard probiotics could in fact produce a whole range of biochemical effects in the liver, blood and urine.  . This will certainly make it much harder for critics to claim that adding just a few bacteria to the diet can’t really make any difference. “We’ve established that friendly bacteria can change the dynamics of the whole population of microbes in the gut,” he says. Not only that, but the study found that different strains could produce quite different responses.
This begins to deal with another of the criticisms of taking probiotics – which is that there is no proper evidence to show which strain is having what effect. Nicholson’s study was done on mice which had had human gut microbes implanted in their own guts, so the set up was highly artificial but it allowed for much more detailed analysis of what was going on. It turned out that one reason why adding a comparatively few bacteria could have such a specific effect was because the Probiotics are commonly referred to as ‘friendly’ or ‘good’ bacteria. They support good health by improving the balance of bacteria within the digestive system…. strains worked with other bacteria to boost the impact. In this case, the biggest influence was in the way the animals metabolised bile acids in the liver – an example of bacteria influencing activity outside the guts. Bile acids emulsify fats in the upper gut, so this research opens the possibility that probiotics could be used to change how much There are many different types of fats; polyunsaturated, monounsaturated, hydrogenated, saturated and trans fat. The body requires good fats (polyunsaturated and monounsaturated) in order to… your body absorbs from your diet.
In fact the link between obesity and gut bacteria has been around for some time, ever since researchers putting rats into in a super-sterile environment from birth, found that without any gut bacteria, these animals stored very little fat – 60% less than usual – even though they ate voraciously. However, once bacteria was allowed in they would start to put on weight; after two weeks they weighed the same as normal rats. Then recently Dr Jeff Gordon of Washington University in St Louis, Missouri, reported that the gut bacteria populations of obese people were dominated by a class known as Firmicutes, while the guts of a lean group had more of another class called Bacteroidetes. So could it be that obesity was linked to an increased ability to absorb nutrients from the gut and was it possible to change that? The possibility that it might be arose when it was found that when obese individuals were placed on a low-calorie diet, the proportion of Bacteroidetes in their guts increased, bringing their gut microbial profile more into line with that of lean people. 
By last summer, Dr Gordon’s team had narrowed the strains responsible for the fat storage down to two key players – one called B.theta and another called M.smithii. Rats with both strains had 13% more body fat than those with either one on its own.  The possibility of manipulating your gut bacteria to save your waistline is creeping closer. . However, attractive as the prospect of weight-loss yoghurt may be, it’s still a long way from the supermarket shelves. It’s another example of a tantalising vision waiting for hard clinical proof. The same is true of a major report from the American Academy of Microbiology.
Probiotic Microbes: The Scientific Basis concluded that “beneficial microbes could represent the future of medicine, with the potential to treat a variety of diseases from diarrhoea and eczema to gum disease and autoimmune disorders.”  Probiotics to stave off colon cancer falls into the same category, as Professor Ian Rowland of Reading University – the leading UK researcher in this field – admitted recently at a probiotics conference in Verona. “There’s good evidence that probiotics can reduce toxic elements in the guts of rats,” he said. “And pretty convincing evidence they reduce the chance of rats’ precancerous cells becoming cancerous. But in humans, we still don’t have the full-scale, placebo-controlled trial to show that they actually reduce cancer risk.”
So what should you be doing to make the most of all the research indicating that a good balance of friendly bacteria in your gut – sometimes known as the microbiome – is essential to your overall health? Of course you could wait until all the evidence from controlled trials was in, but since there is no evidence that probiotics are harmful, it makes a lot of sense to pay attention to your gut’s friendly inhabitants right now. The best place to start is with your diet. According to the authors of a recent review of probiotics: “It’s increasingly being recognised the specific composition of (our gut bacteria), as well as many of its physiological traits. can be modified by relatively small changes in food consumption.”  These changes turn out to be familiar healthy eating advice because our beneficial bacteria aren’t keen on a typical junk food diet high in processed and refined foods. What our two main beneficial bacterial species – Lactobacilli and Bifidobacteria – need us to eat is a diet rich in the Fibre is an important part of a balanced diet. There are two type of fibre; soluble and insoluble. Insoluble fibre helps your bowel to pass… found only in fresh, unprocessed fruit, vegetables and grains.  .
These are the hard-to-digest carbohydrates known, rather confusingly, as prebiotics. The best known and most widely tested are called ‘oligosaccharides’ (oligo = few and saccharide = sugar). They also come in a supplement form often shortened to FOS – fructo-oligosaccharides. Another is ‘resistant starch’, which unlike normal starch, passes through the stomach and can only be broken down in the gut. Other favourite bacterial foods include flavonoids and lignans, found in vegetables, pulses and seeds. Bifidobacteria particularly likes FOS, while another beneficial strain Ruminococcous snacks on the resistant starch. Foods rich in probiotics include chicory, Jerusalem artichokes and soybeans. You can also get prebiotics supplements, which can be especially useful for those not getting enough fruit and vegetables. You need to be careful about taking too much, though. Ten to twelve grams should be enough – more than that can lead to bloating, flatulence and intestinal discomfort.
Prebiotics can also be very useful combined with probiotics if your beneficial bacteria are likely to be under attack. That way you are giving the population a boost along with an added food supply. The number one situation where this is a good idea is when you’ve finished a course of antibiotics; that’s because Lactobacilli and Bifidobacteria are sensitive to a wide variety of antibiotics and so their numbers are drastically reduced following therapy.   They are also useful if you have been under a lot of stress – that could be problems in the office, a hangover or even an operation – because stress can shift the balance in your gut in favour of pathogens such as E.coli and Streptococci and away from Lactobacilli and Bifidobacterium, which grow more slowly. 
Pre and probiotics can also help if you’ve been ill – such as suffering with a bout of cold or flu – and before and after long distance travel. In addition, you might consider giving them to someone who is elderly (good bacteria numbers fall off as we get older) or to a child with an allergy or eczema. A combination of pro and prebiotics in both these groups has proved beneficial. 
Getting the Real Thing
How can you make sure that you are getting probiotics that are going to actually work? In the past there have been scares about supplements that haven’t been properly labelled. One study, for instance, found that eight brands gave the wrong information about either how many bacteria they contained or what strains they were. . So buy from a retailer you’ve reason to trust. Look out for the commonest two strains Lactobacilli and Bifidobacterium because these have had the most research done on them. Sub-strains from these families most commonly recognised as safe include: L. acidophilus, L. rhamnosus, L. plantarum, L. casei, B. bifidum, B. infantis (for babies) and B. longum among others.   It’s worth making a distinction between these strains of bacteria and ones that are used for making yoghurt but aren’t likely to do much good in the gut, like lactobacillus bulgaricus and streptococcus thermophilus. At the moment, yoghurt is the most familiar way of delivering probiotics but these bacteria are likely to be finding their way into all sorts of foods in the future. Research is currently underway, for instance, to find out whether table olives might make a suitable carrier. 
Thirty years ago the evolutionary biologist Richard Dawkins caused a storm when he suggested in his best-seller The Selfish Gene that we humans were nothing more than transport systems for our immortal genes. Realisation of the importance of gut bacteria looks like striking another blow at our self-importance. “The average human should be regarded as a complex ecology rather than as an individual,” Nicholson writes. “Indeed it is tempting to suggest that the role of the host is to function as an advanced fermenter, carefully designed to maximise the productivity of the microbiome.” 
1. M Hickson et al, Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial, British Medical Journal (2007), vol. 335, pp. 80.
2. E B Canche-Pool, Probiotics and autoimmunity: an evolutionary perspective, Medical Hypotheses (2008), vol. 70, issue 3, pp. 657-660.
3. F P Martin, Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model, Molecular Systems Biology (2008), vol. 4, pp. 157.
4. R E Ley, Microbial ecology: human gut microbes associated with obesity, Nature (2006), vol. 444, issue 7122, pp. 1022-3.
5. S Buck, Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut, Proceedings of the National Academy of Sciences (2007), vol. 104, no. 25, pp. 10643-10648.
6. Available from www.asm.org/Academy/index.asp?bid=2093. Click on Clinical, Medical, and Public Health
7. G T Macfarlane, Bacterial Metabolism is a term that is used to describe the chemical reactions that take place within the body’s cells. The body gets the energy it… and health-related effects of galacto-oligosaccharides and other prebiotics, Journal of Applied Microbiology (2008), vol. 104, issue 2, pp. 305-44.
8. M S Donaldson, Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutrition Journal (2004). Vol. 20, no. 3(1), pp. 19.
9. M Claude Barc et al, Effect of Amoxicillin-Clavulanic Acid on Human Fecal Flora in a Gnotobiotic Mouse Model Assessed with Fluorescence Hybridization Using Group-Specific 16S rRNA Probes in Combination with FLow Cytometry. Antimicrobial Agents & Chemotherapy (2004), vol 48(4), pp. 365-1368
10. M W Pletz et al,.Ertapenem pharmacokinetics and impact on intestinal microflora, in comparison to those of ceftriaxone, after multiple dosing in male and female volunteers. Antimicrobial Agents & Chemotherapy (2004), vol. 48(10), pp 3765-72.
11. G S Kelly, Nutritional and botanical interventions to assist with the adaptation to stress. Alternative Medicine Review (1999), vol. 4(4), pp. 249-65.
12. As above.
13. V Coeuret, M Gueguen & J P Vernoux, Numbers and strains of lactobacilli in some probiotic products. International Journal of Food Microbiology (2004), vol. 97(2), pp.147-56.
14. P Bourlioux et al, The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium ‘The Intelligent Intestine’, held in Paris, June 14, 2002, American Journal of Clinical Nutrition (2003), vol. 78(4), pp. 675-83.
15. C Stanton et al, Market potential for probiotics. American Journal of Clinical Nutrition (2001), vol. 73(2 Suppl), pp. 476S-483S.
16. P Lavermicocca et al, Study of Adhesion and Survival of Lactobacilli and Bifidobacteria on Table Olives with the Aim of Formulating a New Probiotic Food, Applied Environmental Microbiology (2005), vol. 71(8), pp. 4233-40.
17. J Nicholson et al, Gut microorganisms, mammalian metabolism and personalized health care, Nature Reviews Microbiology (2005), vol. 3(5), pp. 431-8.