Evidence Based Probiotic Therapy of Proton Pump Inhibitor Induced Dysbiosis

With the emergence of high throughput sequencing techniques, researchers obtained the necessary tools to launch in-depth investigations into the structure and function of the intestinal microbiome. For the first time, it was possible to describe the influence of genetics, environment, nutrition and diseases on the microbiome and identify major determinants. One of the most prominent influencing factors on the composition of the microbiome is the use of proton pump inhibitors (PPI), in the general population as well as in chronic diseases, such as liver cirrhosis.

Proton pump inhibitors are used to treat gastric acid related diseases. They drastically reduce the secretion of gastric acid and thereby increase the gastric pH. The reduction of gastric acid production, however, allows acid-sensitive food-borne and oral bacteria to pass the stomach unharmed and colonize the more distal parts of the intestine. In addition, PPI use creates less favorable conditions for typical gut commensals and reduces the microbial diversity in the intestine. These alterations in the microbiome can be linked to PPI side effects, such as gastrointestinal symptoms (e.g., abdominal discomfort, bloating, constipation or diarrhea) and an increased risk for enteral infections. In patients with liver cirrhosis, PPI-induced changes in the microbiome, namely Streptococcus salivarius and Veillonella parvula - two oral bacteria, are linked to intestinal inflammation and gut permeability and predict a higher risk of complications and a higher three-year liver related mortality. These are considerable risks that need to be weighed against the benefits of the therapy. Reduction of PPI use to cases with a clear indication is one important measure to reduce potential harm of the treatment. However, many patients require long-term treatment, e.g. for gastroesophageal reflux disease or to prevent gastrointestinal bleeding when drugs with a high risk of bleeding are used (such as thrombocyte aggregation inhibitors and oral anticoagulation). Therefore, strategies to reduce oralization and thereby symptoms and negative consequences of PPI are necessary.

One possibility to change the composition of the gut microbiome is the use of probiotic bacteria. Probiotics are live microorganisms that have been demonstrated to alter the gut microbiome and exhibit positive effects on numerous gastrointestinal complaints, strengthen the gut barrier and reduce inflammation parameters. The investigators previously showed in a pilot study that a multispecies probiotic was able to improve gut permeability biomarkers in patients with long-term PPI therapy as well as gastrointestinal symptoms. However, this product was not able to efficiently reverse oralization. Therefore, the investigators conducted a series of experiments, including direct and indirect pathogen inhibition tests to identify probiotic strains that are capable of inhibiting the growth of Streptococcus salivarius and Veillonella parvula in vitro to design an evidence based probiotic mixture. The investigators screened 43 QPS (Qualified presumption of safety, granted by the European Food Safety Authority) certified probiotic strains and identified 5 strains as potential therapeutic agents to prevent/treat PPI induced oralization (unpublished data).