Editorial: further evidence that proton pump inhibitors may impact on the gut microbiota.

Abstract

Proton pump inhibitors (PPIs) such as omeprazole are widely used to treat gastrointestinal disorders, particularly in combating gastro-oesophageal reflux and peptic ulcers. They act by binding to H+/Na+ ATPases in the gut epithelium, and an important consequence of this is to inhibit secretion of gastric acid. They are also used in triple therapies to inhibit gastric Helicobacter pylori. There is increasing evidence, however, for additional changes in the gastrointestinal microbiota resulting from PPIs that may be linked to detrimental health outcomes. It remains unclear whether PPIs cause bacterial overgrowth of the small intestine1 but an increased risk of Clostridium difficile infection in individuals consuming PPIs has been widely documented.2 Clooney et al.3 use a cross-sectional study design to investigate the possible impact of long-term PPI consumption upon the microbial community detected in faecal samples. They find no impact of PPI use on overall bacterial diversity (‘alpha diversity’) but find a decrease in % Gram-negative Bacteroidetes alongside an increase in certain groups of Gram-positive Firmicutes bacteria such as members of the Lachnospiraceae family, notably Blautia spp., and streptococci. This provides further evidence for subtle alterations in gut microbiota composition following PPI use. However, while previous studies have also suggested that PPI use may impact on the gut microbiota,4-6 the observed perturbations have not always been consistent. In contrast to the study by Clooney et al,3 the largest cross-sectional study performed so far6 indicated reduced faecal microbiota alpha diversity following PPI use, and alterations in bacterial groups that largely do not overlap with those observed to be significantly different by Clooney et al.3 Lack of congruence is unfortunately common in the microbiota literature, probably as a result of the large degree of inter-individual variation in microbiota composition, and the often relatively small cohort sizes enrolled in individual studies. Ultimately, we will probably have to move from cross-sectional study designs to larger scale longitudinal cohort studies to better understand the impact of PPIs on microbiota composition and function. We know that C. difficile infection is facilitated by, and accompanied by, a shift in microbial community composition and is inhibited by a restoration of the ‘healthy’ microbial community.7 Thus, impairment of the colonization resistance effect against C. difficile infection provides a possible mechanism to explain the impact of PPIs on infection rates. PPIs appear to have little impact on pH values in the colon.8 Nevertheless, there are other mechanisms through which PPIs might be altering colonic microbial communities. In particular, decreases in gastric acidity could potentially influence micronutrient availability, the digestibility of food components, gut transit and the survival of bacteria from the upper gut and oral cavity. The mechanisms through which PPIs alter the intestinal microbiota and increase C. difficile infections rates, and the connection between these two phenomena, remain to be uncovered. The authors are employed by the University of Aberdeen and would like to acknowledge support from Scottish Government RESAS (Rural Environment Science and Analytical Service). Declaration of personal and funding interests: None.