Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome

Abstract

In recent years, proton pump inhibitors (PPIs) have been criticized for their various adverse interactions and side effects, creating a dilemma among practitioners regarding their use. Our goal is to review the proper use and possible side effects that might be caused by or associated with PPI use. Conclusions were drawn based on the evidence supporting or refuting short-term and long-term adverse events associated with PPI use. We also looked for the evidence regarding effects of PPIs on gut microbiota and their overall safety profile. Although there are significant discrepancies in the current literature regarding various adverse effects associated with PPI use, current data suggest that PPI use is not associated with an increased risk of bone fractures, community-acquired pneumonia, cardiovascular events, hypocalcemia, and gastric malignancies. A mild increased risk of vitamin B deficiency and chronic kidney disease, and a moderate increase in the risk of rebound hypersecretion, small intestinal bacterial overgrowth, and enteric infections, including Clostridium difficile, has been noted with PPI therapy. PPI's link with dementia and spontaneous bacterial peritonitis is not clear and requires further investigation. When used appropriately, PPIs are safe medications and are associated with minimal side effects. A clear indication and potential short-term and long-term side effects should be considered before starting PPI therapy.

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…Moreover, use of PPIs may also increase risk of falls [ 291 , 292 , 293 ]. These associations, however, have not been confirmed in a number of longitudinal studies and reviews [ 259 , 280 , 294 , 295 , 296 , 297 , 298 , 299 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 , 308 , 309 ]; even a modest reduction in fracture risk with PPI use has been reported [ 307 , 310 ]. Some researchers who are not supporting the association of PPI therapy with BMD recognize, nevertheless, that in PPI users the risk of fractures and falls could be higher [ 311 , 312 ] as the unadjusted HR was significantly elevated (1.36, 95% CI 1.19–1.55).…”

The eradication of Helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults

“…The eradication regimen consists of a proton‐pump inhibitor (PPI), bismuth, and two antibiotics. Medications such as PPIs and antibiotics are considered to be the influential contributors in the disruption of gut microbiota composition . Using three independent cohorts (211 PPI users and 1604 nonusers), Imhann et al reported a significant decrease in alpha diversity and changes in 20% of bacterial taxa in PPI users compared with nonusers.…”

“…Medications such as PPIs and antibiotics are considered to be the influential contributors in the disruption of gut microbiota composition. 9,10 Using three independent cohorts (211 PPI users and 1604 nonusers), Imhann et al 11 reported a significant decrease in alpha diversity and changes in 20% of bacterial taxa in PPI users compared with nonusers. Among 1827 healthy twins, Jackson et al 12 also found a significant decrease in alpha diversity and the alteration of bacterial composition in PPI users.…”

Response to Comment on ‘Proton Pump Inhibitors. Risks and Rewards and Emerging Consequences to the Gut Microbiome’

“…We sincerely appreciate your interest and valuable comments on our article published in Nutrition in Clinical Practice. In our paper, we did not suggest that proton pump inhibitors (PPI) use is not associated with community‐acquired pneumonia (CAP).…”