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|Newsletters: Probiotics: Nature Becomes Therapy|
Probiotics: Nature Becomes Therapy
Mark R. Corkins, M.D., C.N.S.P., S.P.R., Co-director of Nutrition Support,
We live our lives surrounded by bacteria. Most of us think of bacteria as causing infection and as bad organisms. Actually, nothing could be further from the truth; we have many bacteria in our lives that are helpful. Without bacteria there would be no cheese or yogurt. We also utilize bacteria that live in our bodies to improve our health. Our lower gastrointestinal (GI) tract is full of bacteria; in fact, more than 500 bacterial species have been cultured from the large bowel.
The idea that bacteria were actually helpful started in 1908, when Metchnikoff reported that Bulgarian peasants who consumed large quantities of sour milk containing the bacteria Lactobacillus bulgaricus lived longer. He coined the term “probiotics,” meaning “for life” and postulated that the bacteria had health-promoting effects.
At birth our GI tract is bacteria-free, but it is quickly filled with bacteria during the birthing process and altered by what we are fed in the first one to two years of life. This collection of bacteria is referred to as our “flora.” Also known as “microbiota,” it most closely resembles that of our mothers, but it is unique to each individual. Why is this important?
The GI tract is one of the most exposed parts of our body. The skin is a major barrier to exterior elements, but the GI tract is constantly exposed to and absorbing things from outside the body. In fact, after bone marrow, the GI tract is the second largest immune organ. The GI lining is full of white blood cells. A balance between bacterial flora and gut-associated lymphoid tissue (GALT) causes a steady state of low-grade inflammation to be maintained in the GI tract, which in turn stimulates the development of and maintains the mucosal barrier in the GI tract. This barrier keeps potential infections and toxins in the intestine out of our blood stream.
Nowadays, we live in a progressively “cleaner” environment. The food we ingest and the substances that come in contact with our bodies have fewer and fewer bacteria. In this era, we are also seeing increasing numbers of autoimmune diseases and infections with unusual organisms. This has led to a “hygiene hypothesis”: decreased exposure to bacteria normally seen in the flora reduces the normal low-grade GI tract inflammation. In other words, the gut’s immune system isn’t busy enough and then ends up making antibodies against its own tissues or substances it should ignore. Also, decreased exposure to bacteria often means there aren’t enough “good” bacteria in the flora to suppress the growth of disease-causing bacteria that can enter our GI tract.
In the last few years we’ve seen an explosion of interest in biotics. Probiotics are living bacteria (dead bacteria don’t do anything). Different bacteria have been shown to do different things and therefore they are not directly interchangeable. For example, studies that use different bacteria can’t be compared with one another because the body responds differently to each bacteria, which makes understanding the total picture very difficult. Some of the commercial probiotic preparations are actually mixtures of several bacteria. To be a probiotic, the bacteria must not cause disease and must result in a health benefit.
Prebiotics are compounds that foster the growth of particular types of bacteria. Studies show that the use of prebiotics results in a shift in the population numbers of bacteria in the GI tract. Prebiotics are usually fibers that we cannot digest, but that the bacteria believed to be beneficial can digest, and use for energy. An example of a prebiotics is fructose oligosaccharide. There is a lot of interest in these agents since they don’t involve living bacteria, and therefore avoid the problem of creating a safe formula that includes living bacteria. There are currently several commercially available enteral formulas that have added prebiotics.
Synbiotics are combinations of living bacteria and prebiotic substances to sustain the bacteria’s growth. The studies with these agents are still very sketchy, although the logic of the combination approach is appealing.
Developments with probiotics, prebiotics, and synbiotics may have important implications for people on nutrition support for several reasons. First, there is a growing realization that many of the infections patients with gastrointestinal problems suffer come from the GI tract itself. Sometimes it appears the balance of the flora is upset, resulting in an overgrowth of bacterial species that in high numbers cause symptoms, such as diarrhea and/or gas. Second, patients with gastrointestinal diseases may have infections in areas outside the GI tract from bacteria normally seen in the GI tract. The term used to describe this is “translocation,” which means bacteria or their toxins present in the GI tract escape and travel through the body via the blood stream.
The growth of appropriate flora can keep disease-causing bacteria in check. It is unclear whether this works by competition (stealing the nutrients or occupying receptors) or if some bacteria actually produce substances that suppress the growth of other bacteria. There is evidence that it could be both mechanisms. Also, as stated earlier, the various bacteria affect the GI immune system. There is new research showing that some of the probiotics actually affect the inflammatory hormones produced by the white blood cells normally located in the GI tract lining. Thus the flora affects how well the GI tract works as a barrier to prevent translocation.
Since each bacterial species is unique, each one produces its own substances and the immune system has an individualized response to each species. It is also apparent that every person responds differently to the same bacteria. Thus every probiotic agent is unique; the response to one does not predict the response to another, and a study using one species cannot be compared with a study using another. This makes research in this area difficult to interpret for clinical use. There are a variety of studies scattered throughout the literature using these agents for a variety of maladies. For this review I chose to focus on literature that has the potential to be helpful to the Oley membership.
The more common families of probiotics are the lactobacilli and bifidobacteria. Each of these is subdivided into multiple species. These bacteria are not disease causing and produce lactic acid as a by-product of their fermentation of materials. Some members of these species have been used in food production to ferment milk and grains to cheese, yogurt, and other foods. These bacteria have been classified by the FDA as “generally recognized as safe” (GRAS) for human consumption. Studies have shown that breast-fed infants have increased numbers of bifidobacteria in their GI tract. Breast-fed infants also have lower rates of infectious illnesses, particularly diarrheal diseases. Although some of this is attributed to the immune factors in breast milk, some is believed to be a result of better flora in the GI tract. Studies have shown that formula-fed infants given probiotics or prebiotics have a change in their flora. The studies show this is only temporary, however, and the flora reverts back after the agent is stopped. Once the flora is established it is quite resistant to change.
Studies have shown that infants with viral gastroenteritis have a shortened illness course if they are given a probiotic. Most of these studies were with Lactobacillus GG (rhamnosus) (see photo). There have also been some studies that indicate that probiotic use may prevent diarrhea from developing.
One of the proposed uses for these agents would be to prevent antibiotic-associated diarrhea. It is assumed that antibiotics change the normal GI flora, which leads to diarrhea. The use of a probiotic to counteract this is logical. There are several small, poorly designed studies in this area. Two meta-analyses suggest that the use of a probiotic with antibiotics could reduce the incidence of diarrhea by up to 60 percent. The best probiotic agents identified in these studies appear to be Lactobacillus GG and Saccharomyces boulardii. There are small studies using other bacterial species, which do not appear to be effective in preventing diarrhea.
Another malady that can result from antibiotic usage is a Clostridium difficile infection (sometimes called C. diff). A lot of people who frequent health care facilities are colonized with this bacterium; the normal flora keeps it in check until antibiotic usage allows it to grow to levels that lead to GI symptoms. Again, this would be a logical intervention area for a probiotic. Only a few studies have been conducted in this area, but it appears that Saccharomyces boulardii reduces the chance of developing a C. difficile infection when taking antibiotics.
Individuals who have had their colon removed and replaced with a surgically created pouch are at risk of developing pouchitis, bacterial overgrowth in the pouch. There are several studies that demonstrate that VSL#3, a cocktail of eight different probiotics, is effective at preventing the recurrence of pouchitis after initial treatment with antibiotics. In fact, this literature is the most convincing of all of the probiotic studies. Interestingly, Lactobacillus GG was found not to be helpful in treating pouchitis.
There are also studies looking at the use of probiotics in inflammatory bowel diseases and in gastrointestinal allergies. However, these studies are very mixed in their quality and agents used, and thus I have not reviewed them in this article.
Probiotics are living bacteria that benefit an individual by helping create a GI flora that resists the growth of disease-causing organisms. Different bacteria behave in different ways, and studies with different agents are not readily compared. A probiotic beneficial against one disease may not be so for another. This field is growing rapidly and administering probiotics has become standard clinical practice in many situations.
For more information on probiotics, borrow the DVD from the Oley featuring Kelly Tappenden’s, PhD, RD talk on Probiotics at the 2007 Oley Regional Conference in Phoenix, AZ.