Irritable Bowel Syndrome Message Boards | Understanding probiotics

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

Print Remind Me Notify Moderator

The Brain, the Gut, the Food, and the Bacteria? Update on Treatment of Functional Gastrointestinal Disorders
Disclosures

Yehuda Ringel, MD Douglas A. Drossman, MD

"The Bacteria
Several studies have suggested a potential beneficial effect of certain probiotics in reducing some of the symptoms of IBS.7

Probiotics vs Antibiotics
In a small (n = 44) study, Faber8 examined the effect of probiotics* alone (n = 20) and in combination with antibiotics (n = 24) on GI symptoms and QOL in an uncontrolled trial of unselected (all subtypes) patients with IBS. Antibiotic treatment included ciprofloxacin* 500 mg twice daily per week, and probiotic treatment included Lactobacillus acidophilus NCFM (10 billion g) and Bifidobacteria infantis (10 billion g) daily for 4 weeks. Both groups showed significant improvement following treatment: In the probiotic/antibiotic group, a decrease in symptom frequency index scores from 35 to 18 (P .001) and an increase in IBS-QOL scores from 67.6 to 87.8 (P .001) were seen; in the probiotic-only group, a decrease in symptom frequency index scores from 39 to 17 (P .001) and an increase in IBS-QOL scores from 69.3 to 86.4 (P .001) were seen. The predominant IBS type did not alter the response to therapy.

Commentary. As a small uncontrolled study, these results may reflect, at least in part, a placebo response. Nevertheless, the findings emphasize the need for additional clinical studies to evaluate the role of probiotics and antibiotics in IBS patients.

Mechanisms of Probiotics
Although the efficacy and role of probiotics in the treatment of IBS remain uncertain and require confirmation, several studies presented during this year's meeting examined possible mechanisms for their effects on GI motor, sensory, and immune function.

Lamine and colleagues9 investigated the effect of treatment with Lactobacillus farciminis bacteria on the nociceptive response to colorectal distension in basal conditions and after TNBS (2,4,6-trinitrobenzene sulfonic acid)-induced colonic inflammation in rats. They found that L farciminis treatment significantly reduced (P .05) abdominal nociceptive response for all distending pressures in both the noninflamed-treated group compared with the noninflamed controls and in the TNBS-induced inflamed hypersensitivity treated group compared with the nontreated group. These researchers attributed this antinociceptive effect to the known ability of L farciminis to produce nitric oxide (NO). Indeed, hemoglobin (an NO scavenger) infusion resulted in reversing this organism's antinociceptive effect. These investigators concluded that a 3-week treatment with L farciminis can reduce visceral pain induced by colorectal distension in basal and inflammatory conditions, and that this effect depends on the NO released by these bacterial strains into the colonic lumen.

In another study, the same group of investigators reported a protective effect of the NO producing-L farciminis against TNBS-induced colitis in rats.10 Rats that were treated with this organism for 3 weeks prior to induction of colitis showed significantly lower inflammation, as expressed by reduction in macroscopic damage score, MPO (myeloperoxidase) activity, and inducible NO synthase activities. As with the previous study, hemoglobin reversed the beneficial effect of L farciminis on the inflammation activity in the colitic rats.

Commentary. These studies suggest a role for NO-producing bacteria in protecting against inflammatory and hypersensitivity conditions. However, these findings in animal models deserve additional investigation in humans in order to confirm beneficial effects.

Another possible mechanism mediating the effects of probiotic bacteria on GI function has been proposed by Verdu and colleagues.11 They investigated the effects of probiotics on intestinal muscle dysfunction in a mouse model of postinfective Trichinella spiralis IBS. Study mice groups were treated with Lactobacillus paracasei, Lactobacillus johnsonii, Bifidobacterium longum, or B lactis. Additional mice received heat-inactivated L paracasei or bacteria-free L paracasei spent culture medium (SCM). At 21 days post infection, L paracasei, but not L johnsonii, showed significant attenuation of hypercontractility to carbachol stimulation, compared with the control group (P = .01). The 2 bifidobacteria strains tended to decrease the hypercontractility; however, this trend did not reach statistical significance (P = .09). The attenuation of muscle hypercontractility was paralleled by a 2-fold decrease in the secretion of interleukin-4 (P .0001), mRNA for transforming growth factor-beta (P = .0001), and cyclooxygenase-2 (P = .001) in longitudinal myenteric plexus preparation and by modulation of genes involved in innate defenses such as RANTES and cryptdin, as evaluated by gene array analysis.

Commentary. It is interesting that the normalization of the postinfection contractility was independent of L paracasei presence in the mucosa-associated flora -- thus indicating that the improvement in intestinal muscle dysfunction by L paracasei and free-L paracasei SCM is likely due to attenuation of cytokine and inflammatory mediator production in the muscularis externa and modulation of innate defense genes in the small intestine. In addition, this effect is strain-dependent.

The importance of the strain-specific effect has also been suggested by findings from other studies.12 The clinical implication for this strain-specific effect has been shown in an interesting abstract presented by Drisko and colleagues.13 These investigators examined 5 commercially, commonly available probiotic products. They used polymerase chain reaction (PCR) gel electrophoresis and amplicon excision with DNA sequencing to determine the bacterial strain content of these 5 products and compared their findings against what was reported in the respective product labeling information.

These investigators found that with a single exception, all bacterial species that were tested were detected in the probiotic samples by PCR analysis and confirmed by DNA sequencing. Bifidobacterium bifidum was not detected in 2 of the 5 samples reporting its presence. In contrast, Lactobacillus spp. were detected in 2 of the 5 product samples for which the species was not listed as an "ingredient."

Commentary. Although cultures of commercially available probiotics closely resemble their labeling information overall, there are some differences. Because emerging data suggest that the beneficial effect of probiotics is strain-dependent, a better regulation of dietary supplements may be necessary to ensure proper preparation and marketing standards."

http://www.medscape.com/viewarticle/456987

I am pretty sure the VSL study was done by the VSL people.

Probiotics Significantly Reduce Symptoms of IBS, Ulcerative Colitis

Martha Kerr

May 21, 2003 (Orlando) � Probiotic therapy, primarily in the form of Lactobacillus acidophilus and Bifidobacteria infantis, significantly improves symptoms and quality of life in patients with irritable bowel syndrome (IBS) and other bowel disorders, researchers reported in a number of presentations here at Digestive Disease Week 2003.

In a study designed to assess the efficacy of probiotics alone or in combination with antibiotics in patients with IBS, Stephen M. Faber, MD, from Albemarle Gastroenterology Associates, PC, in Elizabeth City, North Carolina, evaluated treatment in 44 patients with IBS. Twenty patients received probiotics alone and 24 received ciprofloxacin 500 mg twice daily for one week and two probiotic formulations, Lactobacillus (NCFM) 10 billiong and Bifidobacteia infantis (Bifdo), 10 billiong for four weeks.

Patients completed the IBS-Quality of Life (IBS-QOL) questionnaire and the Symptom Frequency Index (SFI) before and after treatment. For the study group as a whole, IBS-QOL scores averaged 66.2 before treatment and 84.6 after treatment. SFI scores before treatment averaged 38, decreasing to 18 after treatment.

In patients who received both probiotics and antibiotics, IBS-QOL scores averaged 67.6 before and 87.8 after treatment. SFI scores averaged 35 at baseline, decreasing to 18 after treatment.

In the probiotic-only group, baseline IBS-QOL scores were 69.3, increasing to 86.4 after treatment. SFI scores were 39 at baseline and 17 after treatment.

Differences in IBS-QOL and SFI scores between probiotic plus antibiotic treatment and probiotic-only treatment were statistically insignificant, Dr. Faber reported.

A retrospective look at IBS patients treated with probiotics indicates that there is a deficiency of Lactobacillus in the gut flora in patients with IBS, Dr. Faber noted, "but we're not ready to call IBS an infectious disease."

Probiotic therapy also improved symptoms of ulcerative colitis (UC) in a separate study presented by Richard N. Fedorak, MD, professor of medicine and director of the division of gastroenterology at the University of Alberta in Edmonton, Canada.

In a safety and efficacy study of the probiotic formulation VSL3 (VSL Pharmaceuticals, Inc., Ft. Lauderdale, FL), which contains eight lactic acid bacterial species, Dr. Fedorak and colleagues evaluated 30 patients with active mild-to-moderate UC with recent flares. Patients continued with previous treatment that included mesalamine, corticosteroids, and/or azathiaprine, as long as the treatment regimen was stable prior to the study.

Patients took two VSL3 sachets twice a day for six weeks. Ulcerative Colitis Clinical Scores were measured and sigmoidoscopy performed at baseline and after the six-week treatment period.

Dr. Fedorak reported that remission occurred in 63% (19 patients) and there was a clinical response in an additional 23% (seven patients). There was no response in 13% (four patients). Worsening of symptoms occurred in one patient.

Dr. Fedorak said that probiotic therapy was not associated with any adverse clinical or biochemical events.

"I haven't heard of getting into trouble with probiotics," Dr. Faber told Medscape. "These are organisms that are supposed to be in the gut. The body knows how to control them, so it doesn't seem that you can overtreat."

While probiotics have been recognized as beneficial components of food, Dr. Fedorak pointed out that "we don't use it as a food product anymore but as a treatment.

"Infantile diarrhea can be shortened by about a day from the usual three- to four-day course. That is very important in infants. Probiotics are effective with rotavirus symptoms, with antibiotic-induced diarrhea, in pseudomembranous colitis, and perhaps in radiation-induced diarrhea," he said.

But Dr. Fedorak cautioned that "we don't know how they work. They appear to strengthen the mucosal barrier of the bowel and improve immune function. And we don't know which probiotics to use or in what combination."

DDW 2003: Abstract M1582, presented May 19, 20003; Abstract W1523, presented May 21, 2003.

Reviewed by Gary D. Vogin, MD

http://www.medscape.com/viewarticle/455964

Irritable Bowel Syndrome: Physiology and Management
Disclosures

Nicholas J. Talley, MD, PhD

Antibiotics and Probiotics in IBS*
Antibiotic Therapy
Whether antibiotics exacerbate or are protective in IBS is currently highly controversial, with conflicting evidence published in the literature.10,11 Pimentel and colleagues11 reviewed patients with symptoms of IBS presenting for breath testing because of the suspicion of small intestinal bacterial overgrowth. Broad-spectrum antibiotic therapy that reversed abnormal breath testing appeared to improve IBS symptoms in these patients. However, the study was not a randomized, placebo-controlled trial and could be difficult to interpret as it was potentially biased. Pimentel and colleagues12 have followed up their initial work with a new trial evaluating neomycin, a nonabsorbed antibiotic, in IBS. They randomized IBS patients to neomycin 500 mg (n = 49) or placebo (n = 52) twice daily for 10 days. At entry and 7 days after the completion of treatment, subjects returned for a lactulose breath test. Based on an intention-to-treat analysis and defining response as greater than 50% improvement in symptoms, the study authors found that neomycin led to a 39% improvement in IBS symptom scores compared with 12% on placebo. Bowel habit improved in 40% of patients treated with neomycin but in only 15% treated with placebo. Those patients who had an abnormal breath test were the ones who tended to improve. In a separate study, Pimentel and associates13 also showed that a 14-day elemental diet improved an abnormal lactulose breath test in 72% of patients, compared with just 21% of those treated with neomycin.
Moayyedi and colleagues14 have provided some supporting evidence to indicate that antibiotics may be protective in IBS. They reanalyzed a trial of H pylori therapy conducted in symptomatic and asymptomatic patients from the community, aged 40-49 years. Defining IBS by Manning's criteria (ie, 2 of 6 symptoms present), patients given antibiotic therapy (clarithromycin and tinidazole) for H pylori infection were significantly less likely to have a diagnosis of IBS at the end of 2-year follow up (6%) than those who received placebo (9%). However, the number of patients with IBS who initially entered the study and who still had IBS at 2 years was similar in both groups. Of course, this was a hypothesis-generating study, but the concept that antibiotics may protect some patients from IBS warrants more extensive scrutiny.

Commentary
Many questions remain regarding the role of antibiotics in IBS. Do antibiotics change the host intestinal flora and predispose to IBS in some cases, while protecting in others? If antibiotics do benefit patients with IBS, which groups will respond and why? Is therapy required long term, and in whom? Are there safety issues, particularly with broad-spectrum antibiotics, including concern regarding bacterial resistance?
The concept and findings suggesting that antibiotics may be useful for treating patients with IBS will need to be replicated and further investigated before the approach can be recommended.

Probiotic Strategies
Probiotic bacteria compete with pathogenic bacteria and also have anti-inflammatory effects on gut mucosa. For this reason, there has been increasing interest regarding the potential role of probiotics in IBS. Lactobacillus plantarum has been shown to reduce flatulence and abdominal pain but not bloating in IBS.15
Quigley and colleagues16 studied 77 patients with IBS who were randomized to receive either Lactobacillus spp or Bifidobacterium spp, added to a milk drink, for 8 weeks; the control group received the milk drink alone. Subjects who received Bifidobacterium had a significant improvement in pain, bloating, and stools. However, any benefit of Lactobacillus was limited to improvement in pain at only the second and seventh weeks. Hence, probiotic strain specificity may be important in determining the outcome in IBS. Probiotics represent a promising, safe therapeutic class in this clinical setting.

http://www.medscape.com/viewarticle/434526

Inflammation, Infection, and Irritable Bowel Syndrome: An Update

A Role for Probiotics?
Probiotics are live microbial food supplements or components of bacteria that alter the enteric microflora and have a beneficial effect on health. The most frequently used genera are Lactobacilli and Bifidobacteria. The potential mechanisms of their action include competitive bacterial interactions, production of antimicrobial metabolites, mucosal conditioning, and immune modulation. The emerging use of probiotics in several gastrointestinal disorders (eg, inflammatory bowel disease) has led to increased interest in their use in patients with IBS.
Quigley and colleagues6 presented the results of a double-blind, placebo-controlled treatment study with probiotic bacteria in 77 patients (64% female) with IBS. Following a 2-week run-in period off all medication, patients were randomized to receive, once daily, either Lactobacillus spp, Bifidobacterium spp, each added to a milk drink, or the milk drink alone for 8 weeks. IBS symptoms were recorded daily throughout the entire study. In comparison to placebo, subjects randomized to Bifidobacterium experienced a significant reduction in pain, bloating, and bowel movement difficulty. Benefit with Lactobacillus was limited to an effect on pain in weeks 2 and 7 only, and neither probiotic strain had any effect on the frequency of bowel movements. A composite score, incorporating all symptoms, showed significant improvement in response to Bifidobacterium for all weeks. The improvement in the composite score response was greater with Bifidobacterium compared with placebo and Lactobacillus (Bifidobacterium vs Lactobacillus vs placebo = 3.70 +- 0.59 vs 5.25 +- 0.55 vs 5.68 +- 0.56, P .05 for week 4). The symptomatic response with Bifidobacterium was associated with parallel improvement in quality of life as assessed by using an IBS-specific instrument.7,8 A follow-up 4 weeks after discontinuation of the treatment (washout period) showed that both symptoms and quality of life returned to baseline. The results showed a beneficial effect of probiotic bacteria in IBS. However, it must be kept in mind that data on the use of these agents in IBS are still very limited and not always consistent. (For example, a previous double-blind, placebo-controlled, randomized study showed beneficial effect of Lactobacillus plantarium in IBS.9) In addition, as emphasized by the investigators, it seems that the beneficial effect was short-term and strain-specific. Additional information regarding the variability of strain-specific response was provided by the results of a study presented by another group from Ireland, as discussed below.

Sheil and colleagues10 examined cytokine production by human mononuclear cells that were incubated in vitro in various strains of Lactobacilli and Bifidobacteria. They found strain-specific alterations in cytokine gene expression and strain-specific cytokine responses for both Lactobacilli and Bifidobacteria strains. As proposed by the investigators, these results suggest that experiments on the immunomodulatory effects of one bacterium cannot be extrapolated to other bacteria. Thus, each bacterial strain that is considered for use as a probiotic may need to be validated individually.

The results of studies that have thus far been conducted with probiotics are encouraging. However, additional investigations that will better define the potential subgroup of patients, the specific strain, and the duration of treatment are required in order to establish the role of probiotics in the treatment of IBS. Until the latter is accomplished, their use will remain investigational."

http://www.medscape.com/viewarticle/434527

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My website on IBS is www.ibshealth.com

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