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Side effects of proton pump inhibitors (PPI) can be linked to the changes in the intestinal microbiome that occur during therapy, especially in long-term users. Therefore, the microbiome might also be a key player in the reduction of PPI side effects. We tested the effects of a three-month intervention with a multispecies synbiotic on intestinal inflammation, gut barrier function, microbiome composition, routine laboratory parameters and quality of life in patients with long-term PPI therapy. Thirty-six patients received a daily dose of a multispecies synbiotic for three months and were clinically observed without intervention for another three months. After intervention 17% of patients reached normal calprotectin levels; the overall reduction did not reach statistical significance (−18.8 ng/mg; 95%CI: −50.5; 12.9, p = 0.2). Elevated zonulin levels could be significantly reduced (−46.3 ng/mg; 95%CI: −71.4; −21.2; p < 0.001). The abundance of  Stomatobaculum  in the microbiome was reduced and  Bacillus  increased during the intervention. Furthermore, albumin, alkaline phosphatase and thrombocyte count were significantly increased and aspartate transaminase was significantly decreased during intervention. Gastrointestinal quality of life showed significant improvements. In conclusion, microbiome-related side effects of long-term PPI use can be substantially reduced by synbiotic intervention. Further studies are warranted to optimize dosage and duration of the intervention.

The effects of a multispecies synbiotic on microbiome-related side effects of long-term proton pump inhibitor use: A pilot study