A CCEPTED MANUSCRIPT
An exploratory tertile stratification of VCE data showed that the damage induced by ASA occurs
primarily in the first tertile (Figure 3) where a significant Bif195 protective effect (p=0.03) was also
observed (31.0 ± 16.8 au in the Bif195 arm vs 41.6 ± 25.2 au in the placebo arm, Figure 3A and B).
The other secondary endpoints GSRS pain AUC, GSRA total score AUC, plasma I-FABP AUC,
red spots from VCE AUC and serum calprotectin AUC did not meet statistical significance (Figure
4) while fecal calprotectin AUC was significantly lower (p=0.0347) in the Bif195 arm compared to
the placebo arm (Figure 4E.)
ASA and trial product were both generally well-tolerated by the subjects. In total, 32 adverse events
were registered from 22 different subjects included in the n=75 safety analysis set. Twelve of these
adverse events were reported from the Bif195 arm and 20 from the placebo arm (Table 2). None of
the adverse events were related to Bif195 intake, while in total 10 of them were assumed related to
ASA intake, as assessed by the principal investigator. The number of adverse events related to ASA
MANUSCRIPT
did not differ between the two intervention arms (4 and 6 in the Bif195 and placebo arm,
respectively).
DNA sequencing of all fecal samples obtained showed an increase after randomization in
abundance of Bifidobacterium breve in fecal samples obtained from subjects in the Bif195 arm
compared to the placebo arm, confirming trial product compliance (Supplementary Figure 2). The
Bif195 intervention was not associated with significant changes in abundance of specific microbial
taxa nor in the changes of the overall microbiome composition (as revealed by Bray-Curtis
dissimilarity index, Supplementary Figure 3).
Serum PGE2 and TXB2 concentrations showed a robust decline during ASA intake and a reversal
to baseline levels during the final 2 weeks recovery period. The Bif195 intervention did not have
significant effects on these datasets (Figure 5).
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