Das Mikrobiom als Drehscheibe für Nebenwirkungen der Protonenpumpenhemmer-Therapie

Zusammenfassung

Protonenpumpenhemmer werden seit etwa 30 Jahren erfolgreich gegen magensäureassoziierte Erkrankungen, wie peptische Ulzera oder Refluxerkrankungen, eingesetzt. Durch ihre kovalente Bindung an die Protonenpumpen in den Parietalzellen des Magens kann die Magensäureproduktion effektiv reduziert und die therapeutische Wirkung der Protonenpumpenhemmer entfaltet werden. Auf diese Weise wird aber auch ein wichtiger Bestandteil der unspezifischen Immunabwehr ausgeschaltet, der den Körper – und vor allem das Darmmikrobiom – vor mit der Nahrung aufgenommenen Pathogenen oder eingeschwemmten Mundkeimen schützt. Daraus ergeben sich Veränderungen des Darmmikrobioms, wie eine Reduktion der Diversität des Mikrobioms oder eine Fehlbesiedelung des Dünndarms, die mit verschiedenen Nebenwirkungen der Protonenpumpen-(Langzeit-)Therapie, wie einem erhöhten Risiko für Clostridium-difficile-Infektionen oder gastrointestinalen Beschwerden, assoziiert sind. Bei Menschen mit Leberzirrhose bspw. ist die Einwanderung von oralen Bakterien in den Darm mit intestinaler Inflammation und Permeabilität verbunden und kann als Biomarker für das 3-Jahres-Überleben herangezogen werden. Mikrobiomassoziierte Nebenwirkungen sollten daher in den Diskurs über die Risiken von Langzeittherapien mit Protonenpumpenhemmern und dem Abwägen von Alternativen miteinbezogen werden.

Abstract

Proton pump inhibitors are valuable treatment options for gastric acid associated diseases, such as peptic ulcer disease or reflux diseases. Due to their irreversible inhibition of the proton pumps in the parietal cells of the stomach, gastric acid secretion can be effectively reduced. With the reduction in gastric acid, however, proton pump inhibitors also block a highly conserved, crucial part of the unspecific immune system. The gastric barrier protects the body – and here mainly the intestinal microbiome – from food-borne pathogens and oral bacteria that can reach more distal parts of the gastrointestinal tract during proton pump inhibitor therapy. Resulting changes in the intestinal microbiome, such as the reduction in microbial diversity or small intestinal bacterial overgrowth, can be linked to side effects of (long-term) proton pump inhibitor therapy, such as the increased risk of Clostridium difficile infections or gastrointestinal discomfort. In liver cirrhosis patients, the increase in oral bacteria in the intestine is associated with intestinal inflammation and permeability, and can even be used as a biomarker for 3-year liver related mortality. Therefore, microbiome-mediated side effects should be included in the risk assessment of proton pump inhibitor therapy and the evaluation of potential alternatives.

Schlüsselwörter

Mikrobiom - medikamenteninduzierte Dysbiose - PPI-Nebenwirkungen

Key words

drug-induced dysbiosis - PPI side effects - microbiome

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