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Discussion
The trial results indicate that Bifidobacterium breve Bif195 confers significant and objectively
verifiable protection against small-intestinal damage caused by a 6 week ASA challenge in healthy
volunteers. The primary and first secondary efficacy criteria for the trial were met, thereby
highlighting the potential of Bif195 co-treatment in future prevention strategies for a growing
population experiencing silent or overt small-intestinal enteropathy from chronic ASA use.
Although prior studies have described gastric damage from NSAIDs, this is, to the best of our
knowledge, the first trial to record the detailed time-resolved kinetics of ASA-induced, and reversal
of, small-intestinal damage. This dataset shows a gradual increase in damage observed by VCE
during the 6 weeks of daily ASA intake and a partial reversal towards baseline levels over a 2-week
recovery period. Furthermore, the small-intestinal tertile stratification clearly shows that ASA-
induced enteropathy is mainly a duodenal phenomenon. This site coincides with localisation of the
MANUSCRIPT
main effect of the Bif195 intervention on ulceration, further highlighting the potential of protective
intervention with this strain. The strategy to perform serial capsule endoscopies in this trial, enabled
us to obtain the sensitivity needed to observe a significant effect in a dynamic environment where
damage formation and healing co-exists. Thus, it represents a superior and more sensitive form of
assessment than the more usually adopted before/after intervention trial design.
The efficacy of Bif195 in NSAID-associated small intestinal injury may be partly explained by the
difference in pathogenesis between NSAID-associated small intestinal injury and NSAID-
associated gastropathy. Whereas acid and pepsin are the principal luminal aggressors in NSAID-
gastropathy, bile and indeed bacteria are the luminal factors in NSAID-enteropathy 22 . Although pre-
clinical studies in experimental animals have been encouraging, previous trials in humans of
putative probiotics in NSAID-enteropathy have been inconsistent. Certain strains of Bifidobacteria,
are known to strengthen the intestinal epithelium layer, to modulate the local immunoinflammatory
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