Probiotics in Pouchitis
Pouchitis is a nonspecific inflammation of the ileal reservoir, that may appear after surgery for ulcerative colitis, and results in various clinical symptoms. It is a well-recognized long-term complication of restorative proctocolectomy.
The risk of pouchitis increases in patients with a history of extraintestinal manifestations, primary sclerosing cholangitis, positive serology for perinuclear anti neutrophil cytoplasmic antibodies, and backwash ileitis (107).
Pouchitis is associated with bacterial overgrowth and dysbiosis, and antibiotics represent the first-choice treatment. The distal ileum and the large bowel, the sites with the highest bacterial concentration, are the most frequently affected by inflammation. Enteric bacteria or their products have been detected within the inflamed mucosa.
A significant decrease of lactobacilli and bifidobacteria concentrations has been found in ulcerative colitis, Crohn's disease and pouchitis. Lactobacilli as maintenance showed less frequent relapses of pouchitis than those using placebo. Diversion of the fecal stream in the small and large intestine reduces the activity of the inflammation. The luminal contents and purified bacterial products added to isolated intestinal loops trigger systemic and local signs of inflammation.
In a study by Campieri et al. (103), seven patients, after clinical, endoscopic, and histological diagnoses of inflammation of the ileal pouch anal anastomosis with a pouchitis disease activity index (PDAI) > 7, were treated with 2 g/day of rifaximin (a non absorbable antibiotic) and 1 g/day of ciprofloxacin for 1 month.
All patients went into remission during this month, as judged by clinical, endoscopic and histological examination.
After remission, all seven patients were treated with the highly concentrated probiotic mixture VSL3 for nine months. No patient had a relapse in this period. All patients who received placebo had a relapse.
Probiotics in the maintenance of remission of chronic Pouchitis
Gionchetti et al. (108) evaluated the efficacy of VSL#3 in the maintenance of remission of chronic pouchitis. Forty patients in clinical and endoscopic remission were randomized to receive either VSL3 6 g/day, or an identical placebo for 9 months.
The patients were assessed clinically every month and endoscopically and histologically every 2 months or in the event of relapse. Three patients (15%) in the VSL#3 group had relapses within the 9-month follow-up period, compared with 20 (100%) in the placebo group. In the VSL3-treated group, the fecal concentration of lactobacilli, bifidobacteria, and S. thermaphilus increased significantly from baseline levels. These results suggested that oral administration of this new probiotic preparation is effective in preventing flare-ups of chronic pouchitis.
Probiotics in the prevention of the onset of Pouchitis
A positive effect of VSL3 in the prevention of pouchitis has been reported by Gionchetti et al. (109), who compared probiotic therapy with VSL#3 versus placebo in the ability to prevent the onset of acute pouchitis during the first year after ileal pouchanal anastomosis. Forty patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were randomized to receive either VSL3 or an identical placebo immediately after ileostomy closure for 1 year.
Both groups consisted of 20 patients. The patients were assessed clinically, endoscopically, and histologically after 1, 3, 6, 9 and 12 months. Health-related quality of life was assessed using the Inflammatory Bowel Disease Ouestionnaire (IBDO). Two of the 20 patients (10%) treated with VSL3 had an episode of acute pouchitis compared with eight of the 20 patients (40%) treated with placebo.
Treatment with VSL#3 determined a significant improvement in IBDQ score, which was not the case with placebo. During treatment with V8L3, fecal concentration of lactobacilli, bifidobacteria, and S. salivarius increased significantly.
The fecal concentration of Bacteroides, clostridia, coliforms, and enterococci were not modified. This suggested that the beneficial effect was not mediated by the suppression of the endogenous flora. The treatment with V8L#3 was effective in the prevention of the onset of acute pouchitis and improved the quality of life of patients with ileal pouch anal anastomosis.
As mentioned above, probiotic bacteria do not survive for long, and rapidly disappear as soon as the treatment is stopped. Therefore, prophylactic probiotic therapy of pouchitis might require longterm treatment and might not be indicated for all patients.
For this reason, V8L3 would be highly beneficial for patients at high risk of chronic pouchitis. In these cases prophylactic probiotics may be administered, pouch function improved and their quality of life after ileal pouch anal anastomosis could be maintained. Katz et al. (107) suggested that probiotics should be used for maintaining remission in chronic pouchitis and as prophylaxis against pouch inflammation in high-risk patients. Although preliminary results suggest that high doses V8L#3 may improve active pouchitis, probiotic therapy seems to be more effective to prevent mucosal inflammation than to treat it.
Kuisma et al. (110) investigated the efficacy of Lactobacillus GG supplementation as primary therapy for pouchitis and its effect on the microbial flora. Twenty patients, with a previous history of pouchitis and endoscopic inflammation were recruited for a prospective, randomized, double-blind, placebo-controlled trial of Lactobacillus GG supplementation.
Ten patients received Lactobacillus GG and 10 placebo, in two gelatin capsules b.i.d. for 3 months. Quantitative bacterial culture of fresh fecal samples and biopsies taken from the pouch and afferent limb was performed before and after supplementation. Lactobacillus GG supplementation was found to change the pouch intestinal flora by increasing the ratio of total fecal lactobacilli to total fecal anaerobes and enhancing the frequency of lactobacilli-positive cultures in the pouch and afferent limb mucosal biopsy samples.
Only 40% of patients were colonized with Lactobacillus GG, and no differences were observed between the groups with regard to the mean PDAI or the total anaerobes or aerobes of fecal or tissue biopsy samples.
Thus, a single-strain probiotic bacterium supplement of Lactobacillus GG changed the pouch intestinal bacterial flora, but was ineffective as primary therapy for a clinical or endoscopic response. More clinical trials are needed to evaluate the right placement and dosage of probiotics within a treatment regimen for pouchitis.