Stephen Holland, M.D.
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,
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
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.
Stephen Holland, M.D.
Stephen Holland, M.D.
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