A CCEPTED MANUSCRIPT
associated with minimal damage to the small intestinal mucosa and co-administration of antibiotics
reduces NSAID-induced injury 8,7 . Besides the well-established inhibitory effect of cyclooxygenase (COX), ASA specifically has been recognised to compromise the phospholipid layer in mucus 11
increasing access to luminal aggressors like lipopolysaccharide and bile as well as disrupt intestinal
permeability and cause inflammation 12 . Given that deleterious compositional changes to the
microbiota, in addition to direct effects on mucus and epithelial tissue, may increase the risk of
NSAID-enteropathy, we hypothesised that an intervention targeting microbiome-host interactions
may offer an attractive, preventative strategy. Our strain selection was based on the anti-
inflammatory properties of certain bifidobacteria 13,14 and experimental pre-clinical evidence for a role of bifidobacteria in NSAID-associated ulceration 15,16,17 as well as unpublished pre-clinical
screening data suggesting a particular potential of efficacy for the specific strain belonging to this
genus. In addition, another Bifidobacterium breve has been shown to express a pilus-associated
MANUSCRIPT
protein (Tad E) in vivo, but not in vitro , which promotes colonic epithelial proliferation 18 .
Here, we describe the development of a clinical model to assess the quantitative and time-resolved
induction of small intestinal injury upon ASA administration. Using this model, we addressed
whether oral co-administration of a single bacterial strain of Bifidobacterium breve (Bif195) can
reduce the risk of low-dose ASA-induced intestinal ulceration in humans in a randomized, placebo-
controlled, parallel-group, double-blind trial using serial video capsule endoscopy (VCE) as a
rigorous demonstration of efficacy.
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