Integrity of the Gut The intestines are the largest mucosal interface between the environment and us. A single layer of epithelial cells is all that separates the bloodstream and the contents of the intestines. The small intestine has the complex and crucial role of allowing nutrients inside the body while keeping bacteria, toxins, and wastes outside. The tight junctions separating the intestinal cells assume some of these functions. The tight junctions aren’t cemented as previously thought but are rather dynamic structures. Research has revealed that tight junctions are made up of a complex meshwork of proteins, the interaction of which
Understanding Different Strains of Bacteria, Symbiosis, and Why Many Probiotics Don’t Work
The original definition of probiotics was established in 1953 but was somewhat confusing. Today, probiotics simply mean live microorganisms which when reaching the intestines in large numbers will exert positive health effects. Probiotic literally means pro-life or health promoting organisms. There are trillions of bacteria that have set up shop in our intestines (both small and large) and represent a very large and diverse group. Not all of these are friendly; there are a significant number that are hostile such as E. coli or Salmonella or Cryptosporidium that causes food and water poisoning, but overwhelmingly most are friendly.
The Vast Microbiota
Most of us know some of the more popular ones like the acidophilus or Bifidobacterium species that we read on the food labels in the supermarkets. There is however, no such species as Lactobacillus acidophilus regularis that the Danish food giant Danone claims is present in their Activia yougurt. Still, out of the hundreds of kingdoms of strains, there are only four major groups which predominate. This reflects the difficult nature of the conditions in which they must be able to survive, and equally important, the adaptive mechanisms developed by the bugs to survive. This is significant as not every bacteria can survive or colonize. These bugs are collectively referred to as the microbiota, and represent a reserve pool of several million genes, in contrast to the twenty three thousand that human cells collectively provide. Biologists are fond of viewing organisms as part of an ecosystem which includes ALL other organisms, their habitats, food sources, competitors and so on. Likewise, the best way to view these organisms (largely bacteria) is as colonists of our gastrointestinal tract (GIT) forming a complete ecosystem.Each of the bacteria is an individual in its own right; it competes for food and seeks shelter and space with every other organism whether it is a friend or foe. The GIT is a battle zone, and it’s a bug-eat-bug world in there. Furthermore, the organisms communicate with each other as well as the host cells (which they easily outnumber by a factor of ten or more) by means of various cellular signaling systems. This cellular chatter or cross-talk occurs day and night, and is responsible for sensing any changes and danger, so as to allow the bugs to respond appropriately.Our evolutionary system functions in a manner which takes into account the interests of both the host (us) and the bugs, with neither wishing the other any harm. In bad times however, for example, during periods of stress, poor diet, inappropriate lifestyle, indiscriminate use of antibiotics and other pharmaceuticals, exposure to environmental toxins etc., the alignment of interest breaks down and our allies begin to misbehave so as to cause disease. The nature and the range of diseases affected by our gut flora is diverse, from obesity, cancer, allergies, diabetes, and a host of inflammatory conditions such as rheumatoid arthritis and other autoimmune conditions, to disorders like autism.What we tend to forget is that the microbial ecosystem is quite unique and different among people. No two digestive systems are the same. Not only are the inhabitants somewhat different, so are the functions these bugs perform. Because the microbes carry such a large array of genes with them, they are able to carry out many more biological functions than what the human genome allows. For example, many nutrients like milk or the plant based fibers that we consume may not be effectively broken down by our enzymes present in our digestive juices. However, the microbes have no such issues as they have such a large repertoire of genes that can perform far more tasks.
Microbes in Health and Disease
Clearly, the microbes play an important part in disease in terms of both prevention and as a causative factor. Microbes produce chemicals called bacteriocins that can inhibit other nasty bacteria (pathogens). But equally likely, bacteria can and do cause food poisoning, diarrhea, bloating and many other problematic conditions including peptic ulcers, inflammation of the gut, and even cancer.The benefits of probiotics have long been recognized; the Egyptians, Greeks, Romans and subsequent cultures (pun intended) consumed foods treated with bacteria. This is the basis of fermentation techniques, which means letting the bacteria “mellow” the food e.g. cabbage, meats, milk, soy, vinegar, etc. These early food scientists realized that the bacteria was digesting the food and allowing for better availability of nutrients for our bodies. Of course one of the best examples is the yogurt made famous by the residents of the Caucuses and Bulgaria.The role that the bacteria in our gut play in health and disease is becoming more and more recognized and accepted by researchers worldwide. For example, some elaborate experiments by Professor Jeffery Gordon from Washington University in St. Louis have shown that thin individuals have different bacterial mixes than obese populations.1 Interestingly, when individuals changed their diets and lost weight, their gut bacterial ecosystem changed accordingly and was similar to thin individuals.2 This is a significant finding that suggests if the bacterial mix present in thin individuals is given to obese individuals, then obese people may lose weight! In fact Gordon has demonstrated this very point in animals.3The Japanese are world leaders in probiotic and fermentation research. They were the first to study the health benefits of various probiotics for food supplementation back in the 1930’s. Unlike the North American consumer mindset which has been largely brainwashed by industry to focus on the number and the different strains of bacteria present in the probiotic supplement, Japanese companies place greater emphasis on the specifics of the strains and how well researched these strains are in human clinical studies. Not many strains have relevant human data; in fact, over 95% of the products on the North American market have no clinical data and only promote test tube data. Test tube data is somewhat unreliable in regards to extrapolating how these bugs behave in our complex gastrointestinal ecosystem. What should the consumer look for in terms of selecting the right probiotic supplement? The answer in first, second and third place is, “Show me the clinical research; I’m not interested in test tube data or animal studies. Rather, I want to see human data.” One will find that there is a sparse amount of human data. The most likely answer seems to be, “Every other company is offering these strains, and these strains have been used for so long in foods so they must be effective”, or, “We have a study that ten individuals used it and their diarrhea improved or their immune system was boosted”. Unfortunately, these aren’t very convincing answers, and one small human study does not make for a convincing statement. In fact, one needs a number of studies to be conducted to prove the point that the probiotic is indeed beneficial. Moreover, one needs studies with much greater numbers of participants. Most biostaticians (people that determine whether a study has any statistical power and thus if it is of any significance) will tell you that most of these studies prove nothing. No wonder these studies are dismissed by serious researchers. However, there are companies that have researched the right mix of bacteria, using much larger numbers of study participants, and they have done so for 30, 40 or even 50 years! Go with one of these products. Characteristics of a beneficial flora population in the human GIT include: 1) their tolerance to acid, bile and pancreatic enzymes 2) their ability to adhere to the intestinal wall and compete successfully for the Hollywood-like real estate that is our gut 3) their ability to overcome the resistance offered by the existing bacteria present. The normal bacterial residents offer considerable resistance to newcomers via a variety of means including formation of biofilms, crowding out the recent immigrants, altering the pH or by other means 4) their lack of toxicity (the bacteria do not pass on their genes to human cells or develop resistance to antibiotics). Preferably the probiotics ought to be sourced from humans, compatible with other strains present in the supplement. In other words, the bugs don’t eat each other 5) their ability to modulate the immune system rather than cause continual over-stimulation 6) are shelf stable or do not require refrigeration.It is not easy for manufacturers to ensure that their strains meet the above criteria. Of course that doesn’t prevent them from making exaggerated claims, but the truth is out there and some evidence-based products do indeed meet the above criteria. Take the case of TOA, a Japanese company that has marketed a probiotic blend called Bio-Three for over 50 years, and equally important has kept publishing human clinical studies regarding safety and efficacy during that course. The probiotic consists of three lesser known but well researched and documented strains. Two of the strains provide protection against antibiotic-associated or traveler’s diarrhea and Clostridium difficile, anti-inflammatory effects, improvement of the gut barrier, allergy protection and more. The third strain is a food source for the other two, so as to provide nutrients and keep the two functioning optimally. This strategy is unique and provides for a stable, effective and well researched probiotic which has its own food source, alleviating the need to add additional prebiotics like fructo-oligosaccharides that are all too common in many of the probiotics. Furthermore, the number or guessing game isn’t played with such a probiotic; after all, it isn’t the number of CFU’s (colony forming units) present that is important, it is evidence based documentation and compatibility that is critical. One can have twelve billion CFU’s or more, and over a dozen different strains all thrown together but it’s insignificant if there is no research!Probiotics have been successfully used throughout history. In recent times there have been further advances in the isolation, identification and classification of them. By studying their clinical efficacy, probiotics can provide us with additional weapons to keep our gut healthy and protected. However, this cannot happen by chance or by wishing that a bunch of bacteria thrown into a capsule or tablet will work – research is required.
1. Jumpertz, R et-al.Energy-balance studies reveal association between gut microbes, caloric load, and nutrient absorption in human. Am J Clin Nutr. 2011; 94: 58-65
2. Ley R E et al. Microbial Ecology: human gut microbes associated with obesity. Nature. 2006: 444: 1022-1023
3. Turnbaugh PJ et al. Diet-induced obesity is linked to marked but reversible alteration in the mouse distal gut microbiome. Cell Host. Microbe 2008; 17: 213-223Additional References:Shanahan F. Probiotics and inflammatory disease: from fads and fantasy to facts and future. Br J Nutr. 2002; 88: s5-s9Hart A L and Stagg M A. Use of probiotics in the treatment of inflammatory bowel disease. J Clin Gastroenterol. 2003; 36: 111-119Gill HS, Rutherfurd KJ, Prasad J, et al. Enhancement of immunity in the elderly by dietary supplementation with probiotics Bifidobacterium lactis. Am J of Clin Nutr. 2001; 20: 149-156Goektepe I, Juneja VK, Mohamed Ahmedna M, et al. Probiotics in Food Safety and Human Health. CRC Press. 2006