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Probiotics for Inflammatory Bowel Disease (IBD)
Progress reported in Probiotics for IBD,
Crohn & Colitis Foundation of America (CCFA) Sponsors Study
Probiotics were originally used to "beef up" animals, but in the future, they may help people with IBD. Probiotics - are tiny organisms that improve the balance of bacteria in the intestine.
In the 1970s, the agricultural industry began to use probiotics instead of antibiotics (which destroy bacteria) to increase the size and weight of animals. Twenty years later, researchers are investigating the usefulness of these agents in treating several forms of gastrointestinal disease. At an IBD Symposium held during Digestive Disease Week (DDW), Dr. Richard N. Fedorak, MD (University of Alberta), discussed the latest research and promise of probiotics in IBD.
There are many strains of probiotics. Those currently under study for use in IBD include Lactobacilli (GG, acidophillus, and salivarius), Bifidocaterium bifidum, Streptococcus thermophillus, Saccharomyces boulardii and Escherichia coli. Dr. Fedorak, noted that to be effective in treating IBD a probiotic should be:
- of human origin;
- non pathogenic (does not cause disease, e.g., a strain of E. coli that does not cause disease);
- resistant to acid in the upper gastrointestinal (GI) tract;
- capable of adhering to the epithelium (the lining of the intestine);
- able to produces substances that can destroy pathogenic (disease-causing) bacteria;
- able to modulate the immune system.
"Should we expect all strains of probiotics to have the same effect?" asked Dr. Fedorak. "Probably not." They differ in how well they adhere to epithelium, how well they fight bacteria, and how they regulate the immune system. Lactobacilli are able to survive the upper GI tract much better than Bifidobacteria, but Bifidobacteria are better in destroying
pathogenic bacteria. Lactobacilli also have a better profile when you look at immune regulation, so Lactobacilli may be better probiotics for IBD.
Probiotics and the course of IBD
Dr. Fedorak explained how IBD develops, and how probiotics may deter with this process. "You are only going to feel comfortable using probiotics if you understand how they are working," he said, nothing that IBD involves three components:
- an antigen, that is, a bacteria or bacteria product that passes through the epithelium;
- defects in the permeability of the epithelium, possibly because of genetic susceptibility to these
defects, allowing the antigen into the intestine
- a dysregulated immune response that occurs in response to the antigen, also genetically controlled
"In normal individuals the antigen passes through the epithelium and sets up an inflammatory response to eliminate the initiating bacteria," Dr. Fedorak explains. Two types of T-cells interact in the intestine, T-helper1 (TH1) cells, which produce inflammatory cytokines, such as TNF-a, and T-helper2 (TH2) cells, which produce anti-inflammatory cytokines, such as IL-10. TH1 cells respond aggressively to invaders, while TH2 cells restore balance to the immune system in the intestine.
"In people with IBD, the immune system is unable to down-regulate this activated inflammation." The TH1 response gets out of hand. The inflammatory response causes injury to the epithelium, resulting in tissue damage and symptoms that you see as IBD.
What are the mechanisms for probiotics in IBD? "Bacteria adhere to the lining of the colon like icing on a cake," says Dr. Fedorak. "Probiotics are able to negotiate through this layer of bacteria and layer themselves against the epithelial surface. They prevent bacteria from adhering to or crossing the epithelium."
Furthermore, Dr. Fedorak cited a study presented at DDW 2000, demonstrating that probiotics stimulate the immune system. Dr. Liam O'Mahony, PhD, and colleagues (NUI, Cork, Ireland) investigated the effect of Lactobacillus salivarius on human cells in the laboratory. They found that this probiotic enhanced the ability of the epithelium
to inhibit the production of inflammatory cytokines, such as TNF-a. L. salivarius was capable of spurring on the Th2 response, suppressing the inflammatory Th1 response. Of note, the authors studied 15 other strains of lactobacillus that did not elicit this anti-inflammatory response. "You have evidence from a number of laboratories that probiotics are able to fix this immune dysregulation," noted Dr. Fedorak.
"Another important aspect of probiotics is their antimicrobial activity," added Dr. Fedorak. "Probiotics produce a number of agents that destroy bacteria--well over 50 of these agents have been classified. This is particularly important when considering specific bacteria that may be stimulating or initiating
the process in IBD."
Proving the Point
Dr. Fedorak cited five clinical trials that apply this laboratory evidence to the treatment of people with IBD:
- B. J. Rembacken, MRCP, and colleagues (The General Infirmary at Leeds, UK, et al.) reported on a trial of E. coli in active ulcerative colitis (The Lancet, August 21, 1999). They randomly assigned 116 patients to receive steroids and either E. coli or mesalamine. Three months later, 68 percent of group on E. coli were in remission, compared with 75 percent of the mesalamine group. All patients were weaned off steroids, and those in remission were permitted to continue receiving E. coli or mesalamine alone at half the dose. At 12 months, 67 percent of those receiving E. coli had relapsed, along with 73 percent of those receiving mesalamine. "The authors conclude that this probiotic was able to keep a similar number of patients in remission over one year as mesalamine," said Dr. Fedorak, noting that this conclusion should be viewed cautiously. "Patients were receiving low doses of 5-ASA, maybe lower than what you would normally administer to maintain remission, and the rate of relapse at one year was near placebo rates."
- Wolfgang Kruis MD, and colleagues (University of Cologne, Germany) treated 120 patients whose ulcerative colitis was in remission with either E. coli or mesalamine (Alimentary Pharmacology & Therapeutics, October 1997). After three months, 16 percent relapsed in the E. coli group, compared with 11 percent in the mesalamine group. "They conclude that E. coli is similar to this dose of mesalamine in preventing relapse," says Dr. Fedorak. "But this was a limited number of patients, who were only followed for a short time. Again, the dose of mesalamine (1.5 grams/day) was low for maintenance therapy."
- Alessandro Venturi, MD, and colleagues (University of Bologna, Italy) treated 20 patients, also with ulcerative colitis in remission, with VSL-3, a combination of four strains of lactobacilli, three bifidobacteria, and one streptococcus (Alimentary
Pharmacology & Therapeutics, August 1999). "Perhaps this is a good idea, because these probiotic strains are working through different mechanisms," mused Dr. Fedorak. "If one doesn't survive, the other likely will." At 12 months, the rate of relapse was 25 percent, a level that would be expected with mesalamine. "Again, this was an open, unblinded trial [a study where participants know the drug under study, and there is no comparison to another drug or to placebo] of a small number of subjects; it needs to be expanded."
- The lone trial of probiotics in Crohn's was presented at DDW. Mario Guslandi, MD (S. Raffaele Hospital, Milan) treated 32 patients with Crohn's of the ileum or colon in remission, with S. boulardii and mesalamine, or mesalamine alone. At six months, one of 16 patients in the S. boulardii group had relapsed, compared with six of 16 in the mesalamine group. "This is a tantalizing piece of evidence to suggest that this yeast may be effective in maintaining remission in Crohn's," noted Dr. Fedorak, noting once again, however, that this was a small, open trial.
- Dr. Paolo Gionchetti, MD, PhD, and colleagues (University of Bologna, Italy) reported findings on preventing pouchitis using VSL-3, at a Distinguished Abstract Plenary Session during DDW. They administered this probiotic cocktail to 20 patients immediately after the pouch procedure, while 20 others received placebo. Relapse rates at 12 months were 10 percent in the group receiving probiotics, and 40 percent in those receiving placebo. Gerald Friedman, MD, and James George, MD (Mount Sinai School of Medicine, NY), treated 10 patients with unresponsive pouchitis with Lactobacillus GG. All had complete remission of symptoms and damage found on endoscopy.
"These trials show promise, but many are small, open studies," said Dr. Fedorak. "What we can take away from them is that probiotics are safe, with some side effects occurring in people who are immunosuppressed. The problems with probiotics are that we don't understand fully how they work, and that clinical trials are limited. Furthermore, probiotics are being sold over the counter in health food stores, but these products often contains small amounts of or no probiotics. Our ability to standardize and manage this treatment is going to be important.
"What is the future? It's very likely that there will be a preventative role for probiotics in IBD, and perhaps a role in addition to other therapies. We need more clinical trials, and we need to standardize how many organisms to give, what organisms to give, and how they're formulated."
CCFA Sponsors Probiotics Study
CCFA is answering this need: The foundation has awarded a research grant to Athos Bousvaros, MD, at Children's Hospital in Boston, to study the efficacy of Lactobacillus GG in preventing relapse in children with Crohn's disease.
The two-year grant begins July 2000, and will involve ten study sites nationwide. "Preliminary studies suggest that this probiotic may down-regulate inflammatory responses in infants with allergy, and decrease intestinal permeability in children with Crohn's
disease," notes Dr. Bousvaros.
Children with Crohn's currently in remission will be randomly assigned to receive either lactobacillus or placebo, and will be followed for two years. Dr. Bousvaros will compare the groups to see if probiotics prolong remission and decrease the percentage of children
who have flare-ups. "If Lactobacillus GG is shown to be effective in preventing flares of Crohn's, this agent may become first-line therapy for relapse prevention."
We will keep you posted on this exciting area of IBD research. We are in the process of collecting information on the sites involved in Dr. Bousvaros' trial, and will post that information in the IBD Clinical Trials Registry as it comes in.
Medical Reporter & Editor, CCFA
Date Posted: June 30, 2000
Comments from healthcare professionals who have used LB17:
"... I have been using different probiotic blends over the years. The best I found by far is LB17. The ... more
strands of different friendly bateria, the better the probiotic. It has been my experience that LB17 covers every area of body fluids from
the sinuses to the reproductive organs which give LB17 a great advantage over any other probiotic. My patients love the small size of the
capsules and I have used LB17 with great success on open wounds and stubborn acne by ... applying ... directly to the wound.
... be happy to recommend LB17 to any health practitioner."..
Dr. A.W. Martin DC, Ph.D., RNCP, D.N.M. (November 2007)
Dr Martin is a practising nutritionist in Sudbury Ontario with a PhD in nutrition.
"I am a Holistic Therapy Practitioner in the UK .......
Finally, I want to make it clear that I am extremely pleased with the benefits that this product LB17 provides for myself and my clients and
friends who all wish to purchase more of it..."
Ms Helen Rushforth B.A.(Hons), M.A., Flintshire, North Wales, UK (May 2008)
Ms Helen Rushforth is a practising healthcare professional in North Wales, UK
Below is an image of a box of LB17 live probiotic and vegetable soft gel capsule
Each box contains 60 capsules
LB17 live probiotic biomass
LB17 is now also available in paste form without capsules for those who do not or cannot take capsules - see below
Above is a 50gm bottle of LB17 biomass. Next pic is image of the biomass in bulk paste form
The above information is provided for general
educational purposes only. It is not intended to replace competent
health care advice received from a knowledgeable healthcare professional.
You are urged to seek healthcare advice for the treatment of any
illness or disease.
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statements. This product is not intended to diagnose, treat, cure, or prevent