Efficacy of Bifidobacterium breve Fermented Milk in Maintaining Remission of Ulcerative Colitis

Dig Dis Sci. 2018 Jul;63(7):1910-1919. doi: 10.1007/s10620-018-4946-2. Epub 2018 Feb 15.

Abstract

Background: Fermented milk products containing Bifidobacterium breve strain Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients.

Aims: To assess efficacy of BFM in maintaining remission in Japanese patients with quiescent UC.

Methods: This double-blind study (B-FLORA) enrolled 195 patients with quiescent UC, randomized to receive one pack of BFM fermented milk per day [Bifidobacterium breve strain Yakult (10 billion bacteria) and Lactobacillus acidophilus (1 billion bacteria)] (n = 98) or matching placebo (n = 97) for 48 weeks. The primary efficacy endpoint was relapse-free survival (relapse: rectal bleeding score ≥ 2 on Sutherland disease activity index scale for 3 consecutive days and/or initiation of remission induction therapy for worsening of UC).

Results: An interim analysis was conducted after inclusion and follow-up of one-third of patients for the first phase of the study (n = 195). Relapse-free survival was not significantly different between the BFM and placebo groups (P = 0.643; hazard ratio 1.16; 95% CI 0.63-2.14, log-rank test), nor was the incidence of relapse. Therefore, the study was discontinued for lack of efficacy. An exploratory analysis of fecal samples from a subgroup of patients revealed no effects of either study beverage on intestinal microbiota, but there was a significant decrease in Bifidobacterium species before relapse, regardless of treatment group. Three mild adverse events occurred for which a causal relationship with the study beverage could not be ruled out (placebo: abdominal bloating and stress in one patient; BFM: body odor in one patient).

Conclusions: BFM had no effect on time to relapse in UC patients compared with placebo.

Study registration: UMIN000007593.

Keywords: Bifidobacterium breve; Probiotics; Randomized controlled trial; Ulcerative colitis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bifidobacterium breve / physiology*
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / microbiology
  • Colitis, Ulcerative / therapy*
  • Cultured Milk Products / adverse effects
  • Cultured Milk Products / microbiology*
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Intestines / microbiology*
  • Japan
  • Lactobacillus acidophilus / physiology*
  • Male
  • Middle Aged
  • Recurrence
  • Remission Induction
  • Time Factors
  • Treatment Outcome
  • Young Adult

Associated data

  • UMIN-CTR/UMIN000007593