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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\u2010term and long\u2010term 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\u2010acquired pneumonia, cardiovascular events, hypocalcemia, and gastric malignancies. A mild increased risk of vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    deficiency and chronic kidney disease, and a moderate increase in the risk of rebound hypersecretion, small intestinal bacterial overgrowth, and enteric infections, including\n                    <jats:italic>Clostridium difficile<\/jats:italic>\n                    , 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\u2010term and long\u2010term side effects should be considered before starting PPI therapy.\n                  <\/jats:p>","DOI":"10.1002\/ncp.10181","type":"journal-article","created":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T23:40:27Z","timestamp":1533598827000},"page":"614-624","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome"],"prefix":"10.1002","volume":"33","author":[{"given":"Amandeep","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Center for Human Nutrition Diegstive Disease and Survery Institute  Cleveland Clinic Cleveland, Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail A.","family":"Cresci","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and 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