Inflammatory Bowel Disease (IBD) refers to two chronic intestinal disorders: Crohn’s disease and ulcerative colitis. These conditions affect between 2 to 6 percent of Americans, or an estimated 300,000 to 500,000 people.
The causes of Crohn’s disease and ulcerative colitis are not yet well understood, but a leading theory suggests that some agent, perhaps a virus or bacterium, alters the body’s immune response, triggering an inflammatory reaction in the intestinal wall. Many health professionals believe that this virus or bacterium is more likely to exert its disease-causing effect when the body’s balance of friendly bacteria is upset.
The onset for both diseases peaks during young adulthood. An individual with either disease may suffer persistent abdominal pain, bowel sores, diarrhea, fever, intestinal bleeding, or weight loss (wasting disease).
If your doctor thinks you have either Crohn’s disease or ulcerative colitis, a variety of procedures and tests such as endoscopy and barium GI studies are available to confirm disease.
Once diagnosed, treatment options may include medications, dietary changes, and sometimes surgery, to remove diseased bowels. Remission and cure is possible in either condition, but both may persist over an individual’s lifetime. Restoration of the balance of friendly bacteria to the gastrointestinal tract often helps, and is essential to recovery.
Crohn’s Disease
Crohn’s disease primarily involves the small bowel and the proximal colon. It may cause the intestinal wall to thicken and cause narrowing of the bowel channel, possibly blocking the intestinal tract. The result is abnormal membrane function, including nutrient malabsorption.
About 90 percent of patients with Crohn’s disease experience frequent and progressive symptoms of abdominal pain, diarrhea, and weight loss. This can lead to extreme weight loss seen in other wasting conditions such as cancer and AIDS.
The most commonly used drugs to treat Crohn’s are sulfasalazine, prednisolone, mesalamine, metronidazole, and azathioprine.
If a patient does not respond to oral medications, the doctor may recommend surgery. Although surgery relieves chronic symptoms, Crohn’s disease often recurs at the location where the healthy parts of the bowel were rejoined. The length of time that a Crohn’s patient is in remission is not predictable. Again, rebalancing the body’s bacterial populations can help.
Increasing evidence points to an important role for inflammatory cytokines (messenger compounds) for the pathogenesis of Crohn’s disease. One such cytokine, tumor necrosis factor alpha (TNF-alpha), plays a key role in the pathogenesis of intestinal inflammation in Crohn’s disease. (One study showed that release of TNF-alpha by inflamed Crohn’s disease tissues can be significantly reduced by Lactobacillus casei or Lactobacillus bulgaricus supplements, which is a tantalizing though preliminary result).
Ulcerative Colitis
Ulcerative colitis (UC) is an inflammatory disorder affecting the inner lining of the large intestine. The inflammation originates in the lower colon and spreads through the entire colon. Blood in the stool is the most common and distinct symptom of ulcerative colitis. As with Crohn’s disease, doctors diagnose ulcerative colitis by conducting a complete physical exam and other procedures such as barium enema, endoscopy and intestinal biopsy.
Patients with mild or severe ulcerative colitis are initially treated with sulfasalazine. Steroids are usually added in high doses. Other experimental drugs to treat ulcerative colitis include budesonide, tixocortol pivalate enema, and beclomethasone dipropionate enema.
Despite new therapies, an estimated 20 to 25 percent of ulcerative colitis patients will need surgery. Surgery cures ulcerative colitis and most patients can go on to lead normal lives—except some may do so with a colostomy bag. I think it is so important that we first try natural healing pathways.
Probiotics & Inflammatory Bowel Diseases
Richard N. Fedorak, M.D., of the University of Alberta, discussed the latest research on probiotics in inflammatory bowel diseases (IBD) at a symposium during Digestive Disease Week 2000. He notes there are many strains of probiotics under study for IBD, including lactobacilli (GG, acidophilus, and salivarius), Bifidobaterium bifidum, Streptococcus thermophilus, Saccharomyces boulardii, and Escherichia coli (not all E. coli are bad guys; surprisingly, there are also beneficial strains of this species).
Dr. Fedorak noted that to be effective in treating IBD, a probiotic bacteria should be of human origin; nonpathogenic (does not cause disease); resistant to acid in the upper gastrointestinal tract; capable of adhering to the epithelium (the lining of the intestine); able to produce substances that can destroy pathogenic (disease-causing) bacteria; and 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 at destroying pathogenic bacteria. Lactobacilli also have a better profile when you look at immune regulation, so lactobacilli may be better probiotics for IBD.”
Dr. Fedorak explained how IBD develops, and how probiotics may interfere with this process. Referring to both patients and physicians, “You’re only going to feel comfortable using probiotics if you understand how they are working,” he told his audience.
He notes IBD involves three components:
“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-helper-1 (Th1) cells, which produce inflammatory cytokines, such as TNF-alpha, and T-helper-2 (Th2) cells, which produce anti-inflammatory cytokines, such as interleukin-10 (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,” he says. “The Th1 response gets out of hand. That inflammatory response causes injury to the epithelium, resulting in the 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. Liam O’Mahony, Ph.D., and colleagues (at the National University of Ireland, Cork) 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-alpha. L. salivarius was capable of spurring on the Th2 response, while suppressing the inflammatory Th1 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.”
What evidence is there that these agents will work in IBD? In animal models, Dr. Fedorak cited the findings of Levinus Dieleman, M.D., Ph.D., and colleagues at the University of North Carolina, Chapel Hill, who reported that treatment with lactobacillus prevented the relapse of colitis in rat models. This group also has shown that lactobacillus prevents and treats colitis in mice.
Dr.Fedorak cited evidence found in fecal and tissue samples of people with Crohn’s. “There was reduced bifidobacteria in Crohn’s and reduced lactobacillus in ulcerative colitis,” he said. “The worse the disease, the lower the level of probiotics [in the gastrointestinal tract]. There is evidence that probiotics probably play a role in patients with IBD and that giving back those probiotics may be effective in our treatment.”
Dr. Fedorak cited five clinical trials that apply this laboratory evidence to the treatment of people with IBD:
B. J. Rembacken, M.R.C.P., and colleagues from The General Infirmary at Leeds, UK, reported on a trial of a safe strain of E. coli in active ulcerative colitis in the August 21,1999 Lancet. (Some strains like E. coli : h-0157 are highly toxic, but not all, some of which are common to a healthy gut.) They randomly assigned 116 patients to receive steroids and either E. coli or mesalamine. Three months later, 68 percent of the 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 (also known as 5-ASA) 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, M.D., and colleagues at the University of Cologne, Germany, treated 120 patients whose ulcerative colitis was in remission with either E. coli or mesalamine, according to their report in the October 1997 issue of Alimentary Pharmacology & Therapeutics. 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, M.D., and colleagues at the 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, notes their report in the August 1999 issue of Alimentary Pharmacology & Therapeutics.“ 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 presented at DDW 2000 came from Mario Guslandi, M.D., of S. Raffaele Hospital, Milan, Italy, who 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.
Paolo Gionchetti, M.D., Ph.D., and colleagues at the University of Bologna, reported findings on preventing pouchitis using the probiotic “cocktail” 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, M.D., and James George, M.D., of the Mount Sinai School of Medicine, New York, treated 10 patients with unresponsive pouchitis with Lactobacillus GG. All had complete remission of symptoms and damage as found on endoscopy.
“These trials show promise,” 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. In the May 2004 issue of Gastroenterology, we learn, Crohn’s disease, ulcerative colitis, and pouchitis are caused by overly aggressive immune responses to a subset of commensal (nonpathogenic) enteric bacteria in genetically predisposed individuals. Clinical and experimental studies suggest that the relative balance of aggressive and protective bacterial species is altered in these disorders. Antibiotics can selectively decrease tissue invasion and eliminate aggressive bacterial species or globally decrease luminal and mucosal bacterial concentrations, depending on their spectrum of activity. Alternatively, administration of beneficial bacterial species (probiotics), poorly absorbed dietary oligosaccharides (prebiotics), or combined probiotics and prebiotics (synbiotics) can restore a predominance of beneficial lactobacillus and bifidobacterium species. Current clinical trials do not fulfill evidence-based criteria for using these agents in inflammatory bowel diseases (IBD), but multiple nonrigorous studies and widespread clinical experience suggest that metronidazole and/or ciprofloxacin can treat Crohn’s colitis and ileocolitis (but not isolated ileal disease) perianal fistulae, and pouchitis, whereas selected probiotic preparations prevent relapse of quiescent ulcerative colitis and relapsing pouchitis. These physiologic approaches offer considerable promise for treating IBD… These agents likely will become an integral component of treating IBD in combination with traditional anti-inflammatory and immunosuppressive agents.” Many more studies show promise for colitis, too.
How to Use Probiotics for Inflammatory Bowel Diseases
It’s really all very preliminary so be sure to work closely with a knowledgeable health professional familiar in treating these conditions. Taking a standard probiotic or the more exotic strains mentioned in these reports is often beneficial, but do work with a health professional.
I think it is always important to try to duplicate materials and dosages used in clinical studies if you are after a certain curative effect. Although, we also find many instances in which similar but not identical strains (say, two different patented strains of lactobacillus) do equally well, or about as well, at managing the same tasks.