Probiotics, which contain millions of the ‘good-guy’ bacteria, have largely been billed merely as a way to keep the gut healthy. But the latest evidence suggests that the bacteria populating our intestines not only ‘kickstart’ the immune system, but function as an extension of it, a kind of ‘virtual’ organ. New developments in probiotics find them useful for treating all manner of diseases, including cancer.
Your intestines contain billions of living bacteria-10 times the number of cells in your body-and new research suggests that they may be crucial to our immune systems and, thus, our health. In fact, the immune system is not a specific entity in itself, but an interaction between our cells and the ‘foreign’ intestinal flora.
“About 75 per cent of the immune cells of the body are localized to the gut, and almost all immune cells in the body are conditioned in the gut,” says Professor Stig Bengmark of University College London. This conditioning is done by bacteria, 400 of which could fit on the dot of this “i”.
As Professor Fergus Shanahan of the National University of Ireland explains it: “Gut bacteria have a collective metabolic activity equal to a virtual organ within an organ”.
In addition, these bacteria play a vital role in ‘completing’ our genes (see box on the right).
Although these dramatic discoveries about gut flora and the immune system are relatively new, the means by which we can take advantage of them-probiotics-have been around for a century.
First discovered by Nobel prizewinner Elie Metchnikoff in 1907, probiotic yoghurts, drinks and capsules are one of the fastest-growing sectors in food retailing: UK sales are increasing by 40 per cent each year. Most people take them to promote general wellbeing, but now there’s evidence that they can help serious bowel disorders, allergies, cancer and even autism.
The word ‘probiotic’ means simply ‘for life’-in this case, the bacteria that live in our gut. Our intestines are home to around 500 species, some good and some bad. The bad ones such as Escherichia coli, Salmonella and Clostridium are kept in check by the ‘good’ bacteria, mainly lactobacilli and bifidobacteria. And the experts are only now realizing that the presence or absence of gut bacteria at birth could be the key to a range of health problems in later life.
We are not born with a fully functioning immune system. What it needs is exposure to bacteria-almost entirely from the mother. “The birth process allows the progressive formation of complex intestinal microflora composed of myriad bacteria,” says Belgian pediatrician
Dr Jean-Paul Langhendries. “It is used by the young body to initiate its own immune system” (Arch Pediatr, 30 October 2006; epub ahead of print).
So, two things are necessary: natural birth and breastfeeding. Passing down the birth canal exposes the baby to its mother’s bacteria. Some of these may be harmful, but that’s what the immune system needs, according to the latest theory. Then, as the infant breastfeeds, beneficial lactobacilli from the breastmilk enter the baby’s gut to supplant the disease-causing species. This kickstarts the immune system and firmly establishes it-probably for life.
But, modern medicine unwittingly interferes with this process. Infants born by caesarean section or who are not breastfed have a different range of gut bacteria, which can compromise their immune system (Acta Paediatr Suppl, 2003; 91:48-55). Indeed, caesarean-born children have more asthma and food allergies than naturally birthed babies-problems that continue into adulthood (WDDTY vol 17 no 8).
Connection with the brain
But asthma and allergies are just the tip of the iceberg. There is a raft of childhood problems that may be due to a malfunctioning gut-which also affects the brain. Learning difficulties, poor coordination and even autism have been linked with ‘gut dysbiosis’, an imbalance of intestinal bacterial species. One clue is that autistic children have more digestive problems than normal children, as recently confirmed in an in-depth study led by Dr Andrew Wakefield at London’s prestigious Royal Free Hospital, which showed “a consistent profile of . . . increased pro-inflammatory and decreased regulatory activities” in the intestines of autistic children (J Clin Immunol, 2004; 24: 664-73).
How does what happens in the gut affect the brain? The most obvious answer is simple malnutrition. With-out the proper balance within the gut flora, food may be poorly digested and absorbed, leading to nutritional deficiency. Too many ‘bad’ bacteria can also mop up nutrients or, worse, an overgrowth of, say, Candida or Clostridium can produce toxins and create a ‘Catch-22’ vicious circle. The original gut dysbiosis leads to a so-called ‘leaky gut’, where intestinal walls are damaged, thus allowing toxins to pass through into the bloodstream, from where they may then penetrate the blood-brain barrier.
Chief among these toxins are acetaldehyde, alcohol and opiate-like substances from undigested foods. “The theory is that autism is the result of a metabolic disorder,” says Paul Shattock, of the Autism Research Unit at the University of Sunderland. “Peptides with opioid activity derived from . . . foods that contain gluten and casein, pass through an abnormally permeable intestinal membrane and enter the central nervous system to exert an effect on neurotransmission” (Expert Opin Ther Targets, 2002; 6: 175-83).
To test this theory, Professor Glenn Gibson, director of the University of Reading’s Department of Food Biosciences, analyzed the feces of young autistic children, and found abnormally high levels of Clostridium species, confirming Dr Wakefield’s earlier findings.
Gibson then wondered whether giving the children ‘good’, probiotic bacteria would reverse the dysbiosis and reduce their autism. He randomly selected 20 of these children to receive a probiotic capsule containing Lacto-bacillus plantarum, and gave another 20 children an identical placebo capsule. After a few weeks, the chil-dren switched to the other capsule, but neither group knew when they were receiving the real probiotics.
Sadly, the trial soon collapsed. “The effect of the probiotic bacteria was so great that many of the parents realized their children were taking something other than a placebo, and refused to allow the switch to take place,” says Professor Gibson. “Parents told me how the probiotics had made such improvements in their children’s concentration and behaviour that, as one parent said, it would have been heartbreaking to force the children to stop taking them. But it meant I couldn’t draw any firm scientific conclusions from the trial because of the high drop-out rate.”
Nevertheless, Gibson’s ‘results-too-good-to-be-scientific’ trial will be a landmark in probiotic therapy, paving the way for more studies of not only autism, but of the more widespread autistic-spectrum disorders such as Asperger’s syndrome, hyperactivity and learning difficulties in general. Indeed, gut problems similar to those in autism have been seen in children with these related conditions (Am J Gastroenterol, 2000; 95: 2285-95).
Bacteria as therapy
How do probiotics work? Until recently, it was thought their mode of action was simply to stick to the gut wall, preventing other bacteria from gaining a foothold.
But new laboratory evidence suggests that probiotics are much more proactive, producing substances such as acids, bacteriocins and hydrogen peroxide, which can kill harmful bacteria and interfere with their ability to produce toxins (Gut, 2003; 52: 827-33).
Other new evidence (from at least six different studies) shows that probiotics act directly on the immune system, boosting both T-helper and natural-killer (NK) cells, the system’s major weapons. For example, a recent Korean study measured a 35-per-cent increase in NK cells in study participants given probiotics (J Med Food, 2006; 9: 321-7).
Perhaps ironically, a major use for probiotics is to combat the side-effects of their near-namesake-antibiotics. These powerful medicines don’t discriminate between friend or foe, so the inevitable consequence of oral antibiotic therapy is the death of all gut bacteria, good and bad.
Nevertheless, antibiotics may be less efficient at killing the bad species, as they can cause proliferation of one of the worst of them, Clostridium difficile. This stomach bug is fast becoming a major pest of hospitals, as it’s involved in the development of superbug resistance, and has officially been dubbed a ‘new epidemic’ (Ann Intern Med, 2006; 145: 758-64).
However, probiotics have come to the rescue, with over 30 separate studies showing they can halve the incidence of diarrhea caused by C. difficile (Lancet Infect Dis, 2006; 6: 374-82)-not to mention diarrhea in general.
Interestingly, probiotics can cure constipation, too (Best Pract Res Clin Gastroenterol, 2006; 20: 575-87).
With conventional drugs, these contrary effects would be considered impossible. But probiotics don’t act like drugs. They are more like wise regulators, with a unique ability to restore gut bacteria to normal, whatever the state of the intestines.
Bowel disorders-and worse
Probiotics are now offering hope to people who have more serious bowel disorders such as irritable bowel syndrome, which afflicts about 3 per cent of the population. This can flare up for no apparent reason, and cause severe stomach pain, bloating, diarrhea and constipation.
One school of thought says it’s due to food intolerance, but gut bacteria may also be involved, as probiotics have been seen to result in up to a 30-per-cent improvement in symptoms (J Clin Gastroenterol, 2006; 40: 264-9).
Crohn’s disease (CD) and ulcerative colitis (UC), which are also known as ‘inflammatory bowel disorders’, may affect up to a quarter of a million Britons. Orthodox medicine considers these conditions to be essentially incurable. Yet, according to Dr Sandra Macfarlane of Dundee University: “. . . there is now indisputable evidence that a loss of beneficial bacteria is involved in the two conditions.”
Although probiotics are a logical solution, only a few small-scale clinical trials have put them to the test. One, a pilot study at Bologna University, showed that a very high dose of a cocktail of different lactobacilli “induced remission” in two-thirds of CD patients. With UC, however, the results have been mixed. The explanation could be that these trials have tended to use single Lactobacillus species rather than a combination.
“The general experience thus far is that the best effects are obtained with combinations of probiotics rather than single LAB [lactic-acid bacteria] treatments,” says Professor Bengmark.
The most severe form of bowel disease is cancer-of either the colon or rectum. Again, probiotics may be of use here, too. Researchers have noticed an association between a high intake of yoghurt or probiotics and lower rates of colon cancer (J Nutr, 2000; 130: 384S- 90S). So far, trials have shown a significant protective effect of probiotics on colon cancer, and even a tiny curative effect-at least in rats, so it may not apply to humans (Carcinogenesis, 2002;
The link between probiotics and gut conditions is fairly predictable. The real detective work has been to uncover the connections between probiotics and diseases unrelated to the gut.
One breakthrough has involved allergies, perhaps because they are immune-related. The ‘hygiene hypothesis’, for example, posits the idea that allergies are caused by overzealous cleanliness, particularly in childhood-but our immune system needs to be exposed to bacteria to begin working. So far, trials of probiotics involving allergic children and adolescents have generally been disappointing, but some researchers argue that’s because they have been given too late in life to work.
Five years ago, Finnish doctors were the first to examine probiotics in early infancy. Having located more than 100 mothers-to-be with a family history of allergic eczema, they gave their newborns either probiotics or a placebo for the first six months of life. Follow-up of the babies at age two revealed that eczema was halved among those taking the probiotics (Lancet, 2001; 357: 1076-9).
Similar studies on other allergies have had less favorable results, with no particular benefits found in asthma or food allergies and intolerance. This is surprising as one of the major theories of food allergy is the ‘leaky-gut’ hypothesis (mentioned above).
Experts now believe that the answer lies in a huge research program that has been designed to test both individual strains as well as cocktails of lactobacilli. A few small-scale probiotic pharmaceutical companies have already begun testing their own semi-exclusive probiotic cocktails.
As for female urinary tract and vaginal infections, most studies have shown that single probiotics haven’t prevented or cured them, although an Austrian company has found that three Lactobacillus strains (L. rhamnosus GR-1 and L. reuteri B-54 and RC-14) do work (World J Urol, 2006; 24: 28-32). And there’s some tantalizing preliminary evidence of a place for probiotic cocktails in cirrhosis, pancreatitis and postoperative infections, too.
To date, this non-drug therapy is in its infancy. Only a fraction of the 500 gut-flora species has been explored so far, and few but the most advanced researchers understand that the specific strains of bacteria residing in our intestines may be related to maintaining health by keeping particular illnesses at bay.
What’s already clear is that we need to change how we view health and immunity to something that doesn’t just start and end with our own bodies.
Tony Edwards – WDDTY vol 17 no 10 (2007)