Proton pump inhibitors alter the composition of the gut microbiota

Abstract

ObjectiveProton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort.DesignWe investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study.ResultsWe identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut.ConclusionsOur findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences.

Review shows that parental reassurance and nutritional advice help to optimise the management of functional gastrointestinal disorders in infants

“…One review of children up to 18 years of age reported that at least 23% of patients treated with histamine receptor 2 antagonists experienced side effects, as did 34% of those treated with proton pump inhibitors 32. Concerns have been raised with regard to the impact of proton pump inhibitors on the gut microbiome and the association between using proton pump inhibitors and small bowel bacterial overgrowth in children 33, 34. There is sparse evidence for the efficacy of other medication, such as pain relieving agents, prokinetic drugs or over‐the‐counter remedies such as simethicone for treating infantile colic 28, 35, 36, 37, 38.…”

The influence of proton pump inhibitors and other commonly used medication on the gut microbiota

“…5,17 Subsequent gut microbiota studies attributed the increased risk to unfavorable gut microbiota alterations caused by PPI use. [6][7][8] Human, animal and in vitro studies show an overlap between the specific gut microbiota alterations associated with PPI use (as found in Imhann et al Gut 2016) and the bacterial changes that lead to increased susceptibility to Clostridium difficile (as depicted in Fig. 2).…”

“…Bacterial families associated with PPI use in 3 gut microbiota studies. [6][7][8] ; Consistent changes in 2 or all studies are marked in bold; NR D Not reported. Table 3.…”

“…[6][7][8][9][10][11] As a consequence, these types of medication could have an effect on the risk of developing enteric infections or gut inflammation, and they may also have an effect on host metabolism. [12][13][14][15] Susceptibility to enteric infections A well-known example of reduced enteric infection resistance through alteration of the gut microbiota caused by medication is the increased risk of Clostridium difficile infections after (repeated) treatment with antibiotics.…”

“…A small intervention study was published a few months before ours and a similar observational study was published in the same issue of Gut. 7,8 In Table 1, the bacterial alterations associated with PPI use from all 3 studies are presented at the family level. There are many similarities between the results of all 3 studies and, when associations at different taxonomical levels are taken into account (e.g.…”