A CCEPTED MANUSCRIPT
were performed by a third party not otherwise involved in the trial. The labeling of product vials,
based on the randomization list, was also performed by a third-party not otherwise involved in the
trial.
Procedures
Bif195 or placebo were administered in a 1:1 ratio daily to 75 randomized subjects for 8 weeks. To
induce damage to the small intestine, all subjects were co-treated daily with 300 mg of ASA for the
first 6 weeks of the 8 week Bif195/placebo intervention period.
In order to document small-intestinal damage, we performed VCE at 6 visits during the 8 week
intervention period (Suppl. Figure 1 and Suppl. Figure 4). The time course kinetics of ASA-induced
damage, as well as a potentially protective effect by Bif195, were expressed as area-under-the-curve
(AUC) for the 8 week intervention period for all datasets obtained.
MANUSCRIPT
All subjects were given 2 hypromellose capsules daily with or without Bifidobacterium breve
Bif195 starting the day after visit 2 with a duration of 8 weeks. The product stability was monitored
in parallel to trial conduct and showed at least 5*10 10 Colony forming units (CFU) of Bif195 per
daily dose during the period of trial conduct. Detailed trial product and placebo description is
provided in Supplementary Table 1.
All randomized subjects were also given 300 mg of ASA (Alliance Pharmaceuticals, Ireland) to
induce small-intestinal damage. This dose was taken daily from the day after visit 2 with a duration
of 6 weeks.
VCE is the widely accepted reference standard for assessment of occult gastrointestinal bleeding.
Current use include exploration and surveillance of bowel pathology such as in Crohn’s disease,
polyps, small bowel malignancy and drug-induced mucosal injury 19 . To standardise the findings
from VCE, we used a reproducible, clinical scoring system to categorise small intestinal mucosal
damage, the Lewis score. The Lewis score is a validated tool that evaluates villous edema, ulcers
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