Probiotic Studied in Pouchitis

Probiotic is a term that refers to good bacteria that are given to fight disease. Whatever the merits of the term probiotic, we finally have a study that was well done. The study publishedin the journal Gastroenterology was very clear: in a group of patients with the problem of pouchitis there was clear benefit.

I think those are excellent examples of what probiotics have the potential to do. I agree, the data on C. diff colitis looks most compelling to date. The editorial in Gastro this month was prompted by a study that was in the same issue, relating to the use of probiotics in pouchitis, the problem of inflammation in the small intestinal pouch created during ileoanal anastamosis after removal of the colon for ulcerative colitis. To put the horse before the cart, review of the article (by Gionchetti et. al. Oral Bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial) would seem in order.

The study looked at 40 patients with pouchitis all of whom were in remission on drugs. The drugs were then stopped and the 40 patients were then either treated with placebo (maize starch) or a bacterial product called VSL#3 taken twice a day continuously. The trial followed these patients for up to 9 months. In the placebo treated group patients started having relapses after a month, and then all 20 patients eventually relapsed over the next three months, about 2 relapsing each week. In the VSL#3 arm of the study 3 of the 40 patients had relapse over 9 months. Bacteriological evaluation showed that the germs in the stool changed over time with more bifidobacteria, lactobacilli, and strep. salivarius present. The did not subspeciate the bifidobacteria or lactobacilli, however. 

This is the first paper I have seen on bacterial supplementation which is randomized and controlled. As such, it porvides usable data upon which to make medical recommendations. The product used in this trial was shown to provide protection from relapse in the subgroup of patients with pouchitis in the setting of ileoanal anastamosis with chronic pouchitis who had been well controlled on drugs. 85% of patients had a prolonged benefit, compared to 0% on placebo. 

This study provides useful information because it is a controlled study, the patient groups are well described, and sufficient detail is provided to understand the expected benefits of the treatment. The study applies to those with pouchitis who were in remission on medications who took VSL#3. It shows that the bacterial treatment is almost as good as antibiotic treatment for maintenance of remission of pouchitis. (15% failure rate for bacteria versus 5% for antibiotics) The control group was interesting. Maize starch may not have been the best choice of starch. Maize contains certain types of starches that are not digestible by amylase. This means that patients on Maize starch will deliver carbohydrates to the lower intestine, or to the pouch in this case, which could potentially aggravate the pouchitis. Had they used rice starch this would not have been the case. However, the patients selected for the study were patients who were having a lot of relapses anyway.

VSL#3 is an unusual probiotic. It is comprised of 8 different bacteria. Also, they are at very high concentrations and have been freeze-dried. In animal and in-vitro studies single strain mixtures are not able to effectivly change the flora already present in the gut. Also, old studies of germ free animals show that putting in a single germ is generally lethal, but that a mixture of germs is beneficial. These results were the basis for formulating a mixed bacteria supplement. 

These issues raise doubts as to whether single strain bacteria would be as effective as multi strain mixtures. Two studies in ulcerative colitis in the past have shown no benefit with a single strain, but an open label trial suggests there may be some benefit to VSL#3 in UC.

Bacteria are very different from one another, and the diseases Crohn’s, UC, pouchitis, and c. difficile colitis are very different as well. While this mixture now has been shown to work in pouchitis much more needs to be done to determine how well other probiotics work in this and other diseases.

Sartor’s editorial was interesting. After reviewing the study he discussed other studies of probiotics. A strain of E. coli has been shown to have the effectivness of low dose masalamine in maintaining remission in UC. However, there are very few studies of benefits of probiotics. Whether all the strains that were used in this study are needed is not known, and whether other probiotics will help better is not known. Other approaches such as altering the carbohydrates delivered to the gut need to be studied. Sartor also reviewed proposed mechanisms – suppression of resident bacteria, stimulation of gut mucus, prevention of adherence of bad germs, and induction of gut immunity ( including affecting the type of immune response generated ). 

While the editorial was interesting, it did not give blanket support to the use of probiotics. It called for a carefull set of studies so we can understand what probiotics can and cannot do, and emphasized the fact that not all bacterial products are the same. 

If I had pouchitis that had previously responded to treatment I would consider the probiotic if I was one of those few patients with multiple relapses of pouchitis. However, I would expect to need to get the product from overseas and I would then need to take it twice a day forever. This in comparison to taking a course of antibiotics for 10 days three times a year. 

The interesting question is what to do if you are one of the patients that never responded to treatment. Potentially you immune response is different or your flora is different. Whether you would respond to VSL#3 is not known. It would be worth trying, but I would recommend a trial were done under medical supervision in case being such a special patient put you at risk for a flare or other complication when taking that mixture.

The study looked at 40 patients with pouchitis all of whom were in remission on drugs. The drugs were then stopped and the 40 patients were then either treated with placebo (maize starch) or a bacterial product called VSL#3 taken twice a day continuously. The trial followed these patients for up to 9 months. In the placebo treated group patients started having relapses after a month, and then all 20 patients eventually relapsed over the next three months, about 2 relapsing each week. In the VSL#3 arm of the study 3 of the 40 patients had relapse over 9 months. Bacteriological evaluation showed that the germs in the stool changed over time with more bifidobacteria, lactobacilli, and strep. salivarius present. The did not subspeciate the bifidobacteria or lactobacilli, however. 

Author: Stephen Holland

Stephen Holland, M.D. went to medical school at Northwestern University in Chicago, then did his medical residency at Loyola in Maywood (just West of Chicago). He then did research at the University of Alabama at Birmingham, did his GI fellowship there, and went to the University of Illinois at Peoria to teach and do research. He ran a successful private practice for over 12 years in Naperville, Illinois. Most recently he was chief of GI at Mt. Sinai Hospital in Chicago for 5 years.

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