Understanding Probiotics
by Dimitri Papadimitriou
In recent years, a growing body of research evaluating human health has supported the importance of establishing a favorable colonic environment. Much attention has focused on how colonic microorganisms affect human health and nutrition. The human gut contains a diverse array of bacteria that can produce a variety of physiological effects. Some have pathogenic (harmful) effects such as diarrhea, infections, liver damage, carcinogenesis and intestinal putrefaction. Others have health-promoting effects, including inhibition of pathogenic bacteria growth, stimulation of immune function, improvement in digestion and nutrient absorption, and enhanced vitamin synthesis.
At birth, babies have nearly sterile gastrointestinal (GI) tracts, which are soon colonized with large numbers of Bifidobacterium and Lactobacillus, particularly in breast-fed infants. By adulthood, more than 400 different species of bacteria may be present in the gut. Resident bacteria can be found from the mouth through the length of the GI tract. The greatest population is in the colon, where bacteria account for 35 percent to 50 percent of colonic volume.
Bacterial interactions and competition among species is believed to play a major role in the composition of colonic microflora. Generally, for bacteria to colonize the colon they must have the capability to attach to the intestinal epithelium. A microbe's ability to compete for nutrients and adhesion sites on the colonic mucosa largely determines its survival. Diet has also been found to influence bacterial population, as different types of bacteria prefer different nutrient sources. In general, undigested dietary fibers are a good source of nutrients for intestinal bacteria. Fiber resists hydrolysis by the salivary and intestinal enzymes and reaches the colon intact, becoming available for further fermentation by colonic bacteria.
The primary function of the colon is recycling water and disposing of waste by changing food into solid material. The process must happen efficiently before residual matter putrefies and becomes toxic. Also, many pathogenic microorganisms feed off putrefying waste. When beneficial bacteria are present in sufficient numbers, little putrefaction occurs. Bacterioides and Bifidobacterium species appear to possess the versatility necessary for survival in the large intestine and colonization in the colon. These species synthesize a wide variety of polysaccharide depolymerases and glycosilases. As such, they create an environment that inhibits survival of pathogenic bacteria, particularly by forming short chain fatty acids (i.e., propionate, butyrate and acetate) that lower the colon pH, which adversely affects the growth of those pathogens. The acids further neutralize toxic ammonia and lower its concentration in the blood.
Humans have developed a symbiotic relationship with beneficial bacteria. In fact, there are benefits to probiotic (meaning "for life" in Greek) therapies. In the Orient, there is a long tradition of believing health is dependent on food and the importance of beneficial intestinal bacteria. Probiotics may be defined as products containing live organisms that may beneficially affect the host upon ingestion by improving the balance of intestinal microflora.
The effectiveness of probiotics depends on their survival through both the acidic stomach environment and the alkaline conditions of the duodenum, as well as the ability to adhere to the intestinal mucosa of the colon. Probiotics exhibit antimicrobial, immunomodulatory, anticarcinogenic, antidiarrheal and antioxidant activities. Among the specific examples are:
Lactobacillus plantarum improves the recovery of patients with enteric bacterial infections.1 This bacterium adheres to and reinforces the barrier function of the intestinal mucosa, preventing attachment of pathogenic bacteria.
Lactobacillus casei has been demonstrated to increase levels of circulating immunoglobulin IgA in infants infected with rotavirus and correlated with shortening duration of diarrhea due to the virus.2
Lactobacillus GG has been shown to inhibit chemically induced intestinal tumors in rats.3 It has also been found to inhibit the production of pro-inflammatory cytokines.4
Saccharomyces boulardii has been shown to prevent antibiotic-associated diarrhea,5 and also to prevent diarrhea in critically ill tube-fed patients.6
Bifidobacterium lactis results in significant improvement of atopic eczema in children with food allergies.7
There are many probiotic products available, containing various strains individually and in combination. Some products also include a "boost" of food (prebiotics) to enhance the probiotic survival and efficacy. For most individuals, a product delivering 5 billion to 10 billion live bacteria per day is an appropriate dose to maintain a healthy GI environment.8 In the dietary supplement market, most consumers use probiotics for general health and wellness and to address digestive dysfunction. However, some health conditions specifically warrant probiotic ingestion, particularly in cases where the intestinal environment has been appreciably changed. Some of these situations include excessive use of antacids, which change the pH of the intestines; overdoses of laxatives, which reduce normal intestinal peristalsis; and irresponsible use of broadspectrum antibiotics that destroy intestinal microflora,9 which allows pathogenic microorganisms such as staphylococcus, candida or pseudomonas to proliferate.
It is important that manufacturers of probiotic products supply consumers with live microorganisms. In most cases, probiotic bacteria are easily degraded by exposure to heat, oxygen and moisture. Suppliers must control the manufacturing process through use of such products as cryoprotective agents and buffers. Subsequent packaging in moisture impermeable or moisture-resistant containers preferably under inert gas assures product viability.
Quality issues have been researched and approached in two general ways. One calls for formulation of a suitable delivery system, such as using microencapsulation, enteric coating, embedding the bacteria in lipid water-repelling matrices, or buffering the pH. The other approach is directly selecting or modifying the bacteria in a spore form that is more resistant to degradation. Most manufacturers also prefer to use endogenous human strains that exhibit high survival rates, prefer body temperatures for optimal growth and have a strong affinity to adhere to and colonize intestinal walls.
Manufacturers looking to meet label claims should ensure the product contains the right strain in viable quantities and in a proper formulation for the intended use. For example, probiotics in yogurt expire rapidly due to the semiliquid nature of the product; within a month's period all probiotics in yogurt are inactive, even when kept refrigerated.10 In addition, manufacturers should advise both retailers and consumers (through product labeling) of proper storage requirements. Viable bacteria levels as stated at date of manufacture may not be maintained without proper storage.
Despite the difficulties probiotics pose in formulation and quality, consumers will likely be increasingly interested in using these beneficial bacteria as knowledge of the intestinal microflora and its role in maintenance of health and disease resistance advances.
Dimitri Papadimitriou, Ph.D., is with Arevno Consultants. He may be contacted at arevno@aol.com.
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Probiotics & the Digestive Tract
Probiotics have proved to have terrific benefits when it comes to digestive health, especially in terms of clearing up constipation, reducing diarrheic episodes and even reducing the risk of colon cancer.
For constipation, a study conducted in Finland showed the probiotic Lactobacillus rhamnosus (L. rhamnosus) and Propionibacterium freudenreichii, a bacteriocin, produced a 24 percent increase in defecation frequency compared to supplementation with another probiotic, Lactobacillus reuteri (L. reuteri), or a placebo.1
However, L. reuteri, in combination with zinc, has been shown to decrease diarrhea severity,2 as have L. reuteri together with L. rhamnosus in rotavirus patients.3
And a study out of the Universidad de Buenos Aires indicated that of the Lactobacilli Lactobacillus casei (L. casei) and Lactobacillus acidophilus (L. acidophilus), L. casei was more effective in treating bacterial overgrowth in chronic diarrhea.4 For antibioticassociated diarrhea, researchers in London reported Saccharomyces boulardii, also known as Brewer's yeast, and Lactobacilli prevented diarrhea better than placebo.5
L. acidophilus has been shown to survive the GI tract transit in both healthy and diseased people, and it may decrease not only the incidence of pediatric diarrhea, but also reduce the risk of colon cancer.6 L. acidophilus's benefits may come from its ability to stabilize the weak acid environment seen in the GI tract. If Lactobacilli are absent, the pH value moves to the alkaline side and disturbs the function of digestive enzymes.
http://www.endonurse.com/articles/3a1feat1.html
Harvard health
Probiotics: Using Bacteria to Improve Health
We're used to taking antibiotics to defeat an infection. Now evidence from clinical trials suggests that consuming, rather than killing, certain kinds of bacteria might offer a way to treat—and perhaps prevent—some illness. Probiotic therapy or probiotics, as it's come to be called, is especially popular in Scandinavia (particularly in Finland), partly because of the tradition there of eating fermented foods like yogurt.
But as often happens with products marketed as being more natural, probiotics have been oversold. The claims are seductive: pills, powders, and solutions containing "friendly" bacteria will boost the immune system, prevent cancer, and perform assorted other health miracles. This sort of over-the-top hype is easy to spot. But that doesn't mean it's based upon total fiction. All the usual qualifications apply: the studies are small, the results inconsistent, the findings often limited to animal experiments. Nonetheless, the evidence suggests that probiotic therapy could be useful someday as a form of preventive medicine—and not just for diseases affecting the gut.
Why it Might Work
Most of us think of the digestive system as a circuitous food processor. But it's also one of the body's fire walls, keeping out disease-causing microorganisms, as well as proteins that might spur a debilitating immune response, while at the same time letting in vital nutrients.
The gut has considerable help in striking this balance between barrier and conduit: some 500 different kinds of bacteria inhabit a healthy intestine. Collectively they're known as the gut microflora. These "good bacteria" compete with and tend to crowd out disease-causing bacteria by keeping them from attaching to the intestinal wall and secreting agents that the invaders find toxic. The native bacteria also provide protection by stimulating the patches of lymphoid tissue embedded in the wall of the intestine, causing them to churn out antibodies against pathogens. In young children, the microflora are believed to stimulate the growth of the lymphoid tissue itself.
Just as a pollutant can ruin a lake or river, invading viruses or bacteria can lay ruin to this finely balanced intestinal ecosystem. When the invaders win the battle, the gut wall becomes too permeable. Undesirable proteins flood in. The intestine becomes inflamed. Antibiotics can have a similar disruptive effect as they wipe out some of the healthful microflora along with the bacteria that are causing illness.
Prodding the Immune System
Doses of the right kinds of bacteria may also be good for us because they gently stimulate immune systems that have been, in a sense, overprotected. According to the hygiene hypothesis, we may develop allergies and some intestinal problems because we live in relatively germ- and dirt-free environments compared with our ancestors. As a result, our immune systems become overly sensitive and prone to inflammatory responses.
The basic notion behind probiotics is pretty straightforward: restore the depleted ecology of the intestine with new, healthful bacteria. Besides having a good local effect in the gut, this might benefit the immune system as a whole.
Probiotic therapy is also an old idea. Almost a century ago Elie Metchnikoff, director of the Pasteur Institute, argued that Bulgarian peasants lived long lives because they ate yogurt containing Lactobacillus bacteria. In the 1930s, Minoru Shirota, a Japanese physician, maintained that the right mix of gut bacteria could prevent disease. But working out the practical details of these theories hasn't been easy. The lingering questions include which bacteria should be used and who will benefit and under what circumstances?
Effective in Treating Diarrhea
The best results for probiotic therapy have been in children with bad diarrhea.
Infection with rotavirus is the most common cause of severe diarrhea in children. A healthy immune system usually limits a bout of the illness to a few uncomfortable days, but it can last over a week and leave some children so dehydrated that they need to be hospitalized. Finnish researchers, in a series of studies that goes back 10 years, have shown that probiotic therapy cuts the duration of rotavirus-associated diarrhea by 1.4–2.4 days.
Stefano Guandalini, a University of Chicago pediatric gastroenterologist, has published results from a multicenter study in Europe that found value in probiotic therapy for children with diarrhea, regardless of cause. He reported in the January 2000 Journal of Pediatric Gastroenterology and Nutrition that when children hospitalized with severe diarrhea were treated with an oral hydration solution containing Lactobacillus GG, they had a shorter course and a shorter hospital stay than children given the oral solution alone.
When people take antibiotics that alter the gut's microflora, a bacterium called Clostridium difficile often seizes the opportunity, propagates, and produces a toxin. In severe cases, this leads to colitis, an acute inflammation of the lining of the intestine. Two years ago, two large and credible studies, one American and the other Finnish, showed that probiotic therapy reduced the diarrhea experienced by children taking antibiotics for respiratory tract infections. But in other studies of antibiotics, the results have been negative. So the value of probiotic therapy for gut problems caused by antibiotics remains controversial.
The evidence for traveler's diarrhea also ping-pongs. British soldiers traveling to Belize and Finnish tourists visiting Turkey weren't protected by the probiotics they took, according to studies published several years ago. When a different probiotic was tested on tourists from Long Island the diarrhea rate was cut in half.
Useful for Lactose Intolerance
People are lactose intolerant because they don't have enough active lactase enzyme in their intestine to break down lactose, a sugar molecule found in milk. Because they feed on lactose, Lactobacillus bulgaricus, Streptococcus thermophilus, and other kinds of bacteria, either in tablets or in foods like yogurt, have been shown to alleviate the problem. Still, some experts warn that dairy products billed as containing active cultures—such as acidophilus milk—may not be depleted of enough lactose to make a difference for people sensitive to the milk sugar. Pills containing the lactase enzyme itself are available and may, for many, be more effective.
Potential for Bowel Diseases
The results are mixed in research on the effectiveness of probiotic therapies against Crohn's disease, irritable bowel syndrome (IBS), and other bowel disorders. Much of the published research consists of reports on one or several patients, which is the kind of information that yields interesting hypotheses but not good, solid proof of efficacy. But two years ago, Irish investigators reported results from a small, randomized trial that showed Lactobacillus GG reduced the number of unformed bowel movements in IBS patients with diarrhea. But for pain, urgency, and bloating, the probiotics weren't any more helpful than the placebo used in the trial.
Probiotics in Food
Yogurt has been cast as a health food ever since Elie Metchnikoff drew a connection nearly a century ago between the good health of Bulgarian peasants and their consumption of yogurt containing various species of Lactobacillus bacteria.
But, in the early 1980s, Tufts University researcher Sherwood Gorbach and his group conducted a series of experiments showing that the Lactobacillus species commonly found in yogurt (L. acidophilus and L. bulgaricus) didn't colonize the intestine and, therefore, couldn't have much beneficial effect. Not everyone agrees with this point of view—a really steady diet of L. acidophilus might still have some benefits—but it certainly took some of the steam out of the idea that bacterial cultures make yogurt a super health food.
It's not common in the United States, but food makers elsewhere are adding probiotic bacteria to their products. In Australia, for example, a product called Bio-Cheese has added Lactobacillus rhamnosus HN001. Adding bacteria to foods, particularly to dairy products, is feasible. Many of the successful clinical trials of probiotics have used milk laced with bacteria.
You can find reports in the published medical literature suggesting that probiotic therapy might help people with Crohn's disease, but they're preliminary. Bowel disorders are often difficult to treat, so people are going ahead and giving probiotics a try before the definitive studies are done. Some say they're getting good results.
Might Prevent Allergies
A study published in the April 7, 2001, Lancet hinted that probiotics might be used to prevent allergies. Expectant mothers in the treatment part of the study took two capsules of Lactobacillus GG daily for two to four weeks before delivery, which was followed by a six-month course for the infant. Infants who received the bacteria had a rate of chronic allergic eczema half that of infants who didn't. Infants with chronic allergic eczema are at increased risk for having allergies later in life.
Might Boost the Immune System
Various studies have hinted that probiotics might boost the effectiveness of vaccines. Other researchers have shown that they might promote overall health by revving up the immune system. For example, a study published in the June 2, 2001, British Medical Journal found that children attending daycare centers in Helsinki who drank milk spiked with Lactobacillus GG were absent 11% less often and had 17% fewer respiratory infections during the seven-month study than children drinking regular milk.
With age, our immune systems flag. Probiotics might be used to perk them up, according to a study in the December 2001 American Journal of Clinical Nutrition . New Zealand researchers gave 30 healthy volunteers, ages 63–84, milk containing a bacterium called Bifidobacterium lactis HN019 for three weeks. At the end of the study, numbers of several kinds of white blood cells had risen. It's worth noting that this study was sponsored by the New Zealand Dairy Board and that there was no evidence that the higher white blood cell counts improved health.
Which Bugs Work?
The bacteria most commonly used as probiotics fall under the general heading of lactic acid bacteria. These bacteria feed on sugars and produce lactic acid, which is part of the reason they are so useful in the food industry: by generating acid and lowering the amount of sugar, they make foods like yogurt, cheese, and sauerkraut inhospitable environments for disease-causing organisms. Some yeasts, principally Saccharomyces boulardii, have also been used as probiotics.
The bacterial strains tested most often belong to the Lactobacillus and Bifidobacterium genera. So far, researchers have had more success with a strain called Lactobacillus GG than with any other. "GG" is for the initials of the Tufts University researchers who isolated it, Sherwood Gorbach and Barry Goldin. It's also known as Lactobacillus rhamnosus or Lactobacillus rhamnosus GG.
But if you want to buy Lactobacillus GG, it can be hard to find. Gorbach and Goldin have a patent on it, and so far, it's available commercially only in a product called Culturelle, which is sold through a Web site and a toll-free phone number.
The strains that are used in commonly available probiotics include L. acidophilus and L. reuteri. Whether L. acidophilus, even in large doses, can populate the gut is doubtful. L. reuteri has shown some promise as a treatment for childhood diarrhea.
Researchers and companies are competing to show that their particular bacterial strain works best. Some are placing their bets on combinations. For example, VSL Pharmaceuticals, a Gaithersburg, Md. company, is selling a product called VSL #3 that contains eight different kinds of bacteria.
http://www.health.harvard.edu/hhp/article/content.do?id=549
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My website on IBS is www.ibshealth.com
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