| Summary: | Proton pump inhibitors (PPIs) are commonly prescribed medications associated with changes in the gut microbiome and dysbiosis when used long-term. Probiotics, such as Enterogermina<sup>®</sup> (containing four strains of <i>Bacillus clausii</i>) reduce side effects from triple therapy with PPI+antibiotics. We aim to assess the ability of this probiotic in preventing and/or treating the dysbiosis induced by PPI use. Faecal samples from six healthy donors were used to colonise a Triple-Mucosal-Simulator of the Human Intestinal Microbial Ecosystem<sup>®</sup> model with added ileal compartment. Changes in the microbial community composition and metabolite production were measured for PPI alone (control), PPI+Enterogermina (preventative), and Enterogermina treatment after PPI (curative). Differences were assessed by one-way ANOVA with Tukey’s multiple comparisons test. The model was shown to replicate some of the effects of long-term PPI use. There were significant changes in microbial diversity and an increase in butyrate levels in the preventative and curative arms, indicative of a beneficial effect to gut health. Probiotic use countered some of the effects of PPI use: <i>Streptococcus bovis</i> levels increased in the control arm but reduced following probiotic treatment. These results show that probiotic treatment with <i>B. clausii</i> may have beneficial effects on the gut microbiota following PPI treatment.
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