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Is There a Role for Probiotic Therapies in Inflammatory Bowel Disease?
billion micro-organisms of B. breve, B. longum, and L. acidophilus as both Pouchitis
an induction and a maintenance treatment in patients with UC. Kato et al. Typically, patients with pouchitis have a history of ulcerative or
randomized 20 adults with UC to receive either BFM or placebo. indeterminate colitis, have had a colectomy, and have had a loop of distal
Concomitant 5-aminosalicylates were allowed. After three months of ileum pulled down to the anus and folded on itself in an attempt to create
therapy, there was a statistically significant reduction in clinical disease a reservoir. In approximately 30% of patients with UC who have undergone
severity in both the probiotic and placebo groups, but a greater decrease in this surgery, inflammation will recur inside the neorectum. Regardless of the
endoscopic severity in the BFM group.
6
Another study randomized 21 pre-surgical findings, patients with inflammation and ulceration limited to
patients with UC on salicylate maintenance therapy to BFM versus placebo the pouch are classified as having ‘pouchitis,’ whereas patients who develop
for one year. Investigators reported a 27% rate of clinical relapse in the BFM pouch fistulae, granulomatous inflammation of the pouch, or inflammation
group, and a 90% relapse rate in the control group.
7
of the ileum above the pouch are classified as having ‘Crohn’s disease of the
pouch.’ Interestingly, patients with familial polyposis who undergo the same
surgery rarely develop pouch inflammation, again suggesting that pouchitis
is a gene–microbe interaction.
A second agent examined is the probiotic
yeast Saccharomyces boulardii. This
The probiotic VSL#3 is a packet that contains eight strains of live bacteria,
including four strains of Lactobacillus, three strains of Bifidobacteria, and one
yeast has proven efficacy in the
strain of Streptococcus thermophilus. One packet contains approximately
prevention of recurrent Clostridium
450 billion bacteria. Gionchetti et al. conducted a randomized, double-blind,
placebo-controlled trial randomizing patients with pouches to either VSL#3
difficile infection.
(900 billion bacteria) or placebo. The probiotic was administered immediately
after ileostomy closure, prior to the development of pouchitis. Over one year
of follow-up, two of 20 patients randomized to VSL#3 developed a clinical
A second agent examined is the probiotic yeast Saccharomyces boulardii. flare compared with eight of 20 patients on placebo.
12
A separate study
This yeast has proven efficacy in the prevention of recurrent C. difficile by Mimura et al. in 36 patients with active pouchitis utilized initial
infection, as documented by open-label and randomized controlled trials. In induction therapy with ciprofloxacin and metronidazole and subsequent
an open-label study, Guslandi et al. administered S. boulardii 250mg three randomization to either VSL#3 or placebo. Over one year of follow-up, 17 of
times a day for four weeks to UC patients flaring despite mesalamine. They 20 patients on VSL#3 remained in remission compared with one of 20
reported clinical improvement, with a decline in Rachmilewitz activity score patients on placebo.
13
The above data are fairly convincing that VSL#3 may
to level <5 in 17 of 25 patients and with one patient worsening during the have a role in the prevention and treatment of mild antibiotic-responsive
study period.
8
pouchitis. It is unclear whether it is of any benefit in more severe pouchitis,
steroid-dependent pouchitis, or Crohn’s disease of the pouch.
A pilot study of the polymicrobial preparation VSL#3 (see ‘Pouchitis,’
below) assigned 32 patients with ‘active UC’ to six weeks of VSL#3
treatment. Concomitant therapy allowed in the trial included oral or
rectal mesalamine, oral or rectal corticosteroids, or 6-mercaptopurine/
azathioprine. The mean UC clinical activity score of patients at entry
A number of studies have raised the
into the study was approximately 6.5. Eighteen of 32 patients
question of altered microbial flora in
entered remission (defined as an activity score of <2) during the six-week
study period.
9 patients with Crohn’s disease.
The largest clinical trial concerning UC published thus far randomized
116 patients with active UC to induction with corticosteroids, plus
administration of either the probiotic E.coli nissle 1917 (5x10
10
Crohn’s Disease
bacteria/day) or mesalazine for one year. Not surprisingly, since both A number of studies have raised the question of altered microbial flora in
groups were induced with prednisone, initial response rates were similar. patients with Crohn’s disease, with reports of high mucosal bacterial
In follow-up over one year, the time to relapse was identical in the E. coli count, decreased Bifidobacteria spp., and increased E. coli spp.
14–17
and mesalazine groups. However, the maintenance dose of mesalamine However, probiotic trials in patients with Crohn’s disease have largely
used in this study was low—only 1.2g per day. Thus, it is unclear whether failed to show a significant effect. Our group conducted a clinical trial of
either the E. coli or the low-dose mesalazine in this study would have Lactobacillus GG (LGG) as adjunctive maintenance therapy in 75 children
been superior to placebo.
10
with Crohn’s disease. The primary inclusion criteria were Crohn’s disease
and clinical remission, defined by a pediatric Crohn’s disease activity
Another large three-arm study, published in abstract form, randomized index of <10. Patients received either LGG (10 billion units twice per day)
approximately 150 patients to placebo, L. salivarius, or B. infantis powder. or placebo in addition to their standard maintenance therapy for up to
Patients took the probiotic supplement for one year. At the end of two years. Amino-salicylates, 6-mercaptopurine, and azathioprine were
the follow-up period, there was no difference in relapse rates between the allowed as concomitant therapies. Relapse rates and time to relapse
three groups.
11
were not significantly different between the two groups.
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US GASTROENTEROLOGY 49
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