P478 The current place of probiotics in treatment of pouchitis: systematic review
Authors: Lichtenstein L. , Avni I. , Ben-Bassat O. 
Published: February 2017

Abstract
Background: Pouchitis is a common complication in patients undergoing restorative proctocolectomy for ulcerative colitis. Therapeutic attempts include manipulations of pouch flora composition. In this systematic review, we aimed to score the evidence supporting the use of probiotics and prebiotics in pouchitis patients, to clarify the place of these treatments in current therapeutic regimens.
Methods: We conducted extensive electronic searches of the PubMed and SCOPUS databases, from their earliest records through Nov 2016, for MESH terms “probiotics” and “pouchitis”.
Results: The electronic search retrieved 20 citations [1–20]. Six published RCTs [2,3,9,10,13,14] and a RCT presented as an abstract [12] evaluated clinical, endoscopic end/or histological effect of probiotics as a primary outcome; other reports ranged in level of evidence between meta-analyses [16–19] (4), open-labeled trials [1,4–8,11,15] (8) and letters [20] (1).
Conclusions: Prevention of onset of pouchitis/Primary prevention. Three studies examined the ability of various probiotic regimens to prevent the onset of pouchitis after the restorative proctocolectomy [1–3]. Primary preventive effect of VSL#3 was indicated by a single RCT, with calculated effect ratio of 1.50 [1.02, 2.21] [16].
Table 1. Use of probiotics for prevention of onset of pouchitis Study No. of patients Duration (months) probiotic strain Strain Control Pouchitis-free survival Gosselink (2004) 117 36 LGG No treatment (historical control) 93% vs. 71% (p=0.011) Gionchetti (2003) [2] 40 12 VSL#3 Placebo 90% vs. 60% (p&lt;0.05) Yasueda (2015) [3] 17 24 Clostridium butyricum Placebo 89% vs. 50% (NS)
Treatment of acute episode. Seven – mostly open-labeled and uncontrolled – trials examined the use of probiotics for treatment of acute pouchitis episode [4–10]. Efficacy of probiotics in acute episodes of pouchitis needs to be proved in randomized controlled trials.
Table 2. Use of probiotics for treatment of active pouchitis Study No. of patients Duration (months) Strain Control Outcome Gionchetti et al. (2007) [4] 23 1 VSL#3 Open-labeled; uncontrolled 69% remission rate Laake et al. (2005) [5] 51 (10 with active disease) 1 Cultura® fermented milk product Open-labeled; uncontrolled Symptomatic and endoscopic improvement in patients with active disease Laake et al. (1999) [21] Cultura® fermented milk product Open-labeled; uncontrolled Symptomatic improvement Laake et al. (2003) [7] 10 ½ month Cultura® fermented milk product Open-labeled; uncontrolled Endoscopic improvement Laake et al. (2004) [8] 41 UC + 10 FAP 1 Cultura® fermented milk product Open-labeled; uncontrolled Symptomatic remission and endoscopic improvement Tomasz et al. (2014) [9] 43 (14 with active disease) 9 Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. Bulgaricus, Bifidobacterium bifidus Placebo 43% remission rate vs 0% on placebo Kuisma (2003) [10] 20 3 LGG Placebo No benefit
Seven studies aimed to determine the efficacy of probiotic strains in preventing recurrences in patients with previous episode/s of pouchitis [4,9,11–15]. Probiotic mixture VSL#3 effectively prevents relapses after successful antibiotic treatment of active inflammation, with calculated effect ratio of 20.24 [4.28, 95.81] [16]. Side effects may affect the adherence of the patients with the long-term treatment [15,16].
Table 3. Use of probiotics for prevention of recurrences of pouchitis Study No. of patients Duration (months) Probiotic strain Control Outcome Pronio (2008) [11] 31 12 VSL#3 No treatment Small reduction of PDAI scores Brown (2004) [12] (abstract) 17 6 Bifidobacterium longum BB-536 Placebo Pouchitis-free survival 86% vs. 60% on placebo (NS); small reduction of PDAI scores Tomasz et al. (2014) [9] 43 9 Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. Bulgaricus, Bifidobacterium bifidus Placebo 43% in remission vs 0% on placebo Gionchetti et al. (2007) [4] 16 6 VSL#3 Open-labeled; uncontrolled 69% remission rate Gionchetti (2000) [13] 40 9 VSL#3 Placebo Pouchitis-free survival 85% vs. 0% on placebo (P&lt;0.001) Mimura (2004) [14] 36 12 VSL#3 Placebo Pouchitis-free survival 85% vs. 6% on placebo (P&lt;0.0001) Shen (2005) [15] 31 8 VLS#3 (self administration) Open-labeled compliance trial 80% non-adherence; 74% self-reported recurrence of symptoms
References:
[1] Gosselink, M.P., et al., Delay of the first onset of pouchitis by oral intake of the probiotic strain Lactobacillus rhamnosus G.G. Dis Colon Rectum, 2004. 47(6): p. 876–84.
[2] Gionchetti, P., et al., Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology, 2003. 124(5): p. 1202–9.
[3] Yasueda, A., et al., The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis. Surg Today, 2015.
[4] Gionchetti, P., et al., High-dose probiotics for the treatment of active pouchitis. Dis Colon Rectum, 2007. 50(12): p. 2075–82.
[5] Laake, K.O., et al., Outcome of four weeks' intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-analanastomosis in ulcerative colitis. Scand J Gastroenterol, 2005. 40(1): p. 43–51.
[6] Laake, K.O., et al., Influence of fermented milk on clinical state, fecal bacterial count and biochemical characteristics in patients with Ileo-Pouch-Anal-Anastomosis. Microb Ecol Health Dis, 1999. 11: p. 211–7.
[7] Laake, K.O., et al., Assessment of mucosal inflammation and circulation in response to probiotics in patients operated with ileal pouch anal anastomosis for ulcerative colitis. Scand J Gastroenterol, 2003. 38(4): p. 409–14.
[8] Laake, K.O., et al., Assessment of mucosal inflammation and blood flow in response to four weeks' intervention with probiotics in patients operated with a J-configurated ileal-pouchanal-anastomosis (IPAA). Scand J Gastroenterol, 2004. 39(12): p. 1228–35.
[9] Tomasz, B., et al., Long-term use of probiotics Lactobacillus and Bifidobacterium has a prophylactic effect on the occurrence and severity of pouchitis: a randomized prospective study. Biomed Res Int, 2014. 2014: p. 208064.
[10] Kuisma, J., et al., Effect of Lactobacillus rhamnosus GG on ileal pouch inflammation and microbial flora. Aliment Pharmacol Ther, 2003. 17(4): p.509–15.
[11] Pronio, A., et al., Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm Bowel Dis, 2008. 14(5): p. 662–8.
[12] Brown, S.J., et al., Bifidobacterium longum BB-536 and prevention of acute pouchitis. Gastroenterology, 2004. 126(4 Suppl 2): p. S465.
[13] Gionchetti, P., et al., Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology, 2000. 119(2): p. 305–9.
[14] Mimura, T., et al., Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut, 2004. 53(1): p. 108–14.
[15] Shen, B., et al., Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: experience in clinical practice. Aliment Pharmacol Ther, 2005. 22(8): p. 721–8.
[16] Singh, S., et al., Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev, 2015. 11: p. CD001176.
[17] Shen, J., Z.X. Zuo, and A.P. Mao, Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn's disease, and pouchitis: meta-analysis of randomized controlled trials. Inflamm Bowel Dis, 2014. 20(1): p. 21–35.
[18] Elahi, B., et al., On the benefit of probiotics in the management of pouchitis in patients underwent ileal pouch anal anastomosis: a meta-analysis of controlled clinical trials. Dig Dis Sci, 2008. 53(5): p. 1278–84.
[19] Holubar, S.D., et al., Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev, 2010(6): p. CD001176.
[20] Kuzela, L., M. Kascak, and A. Vavrecka, Induction and maintenance of remission with nonpathogenic Escherichia coli in patients with pouchitis. Am J Gastroenterol, 2001. 96(11): p. 3218–9.