Proton pump inhibitors decrease diversity in gut microbiome, increase risk for complications

"Evidence has been mounting for years that long-term use of proton pump inhibitors poses increased risks for a variety of associated complications, but we have never really understood why," says John DiBaise, M.D., a Mayo Clinic gastroenterologist and senior author on the study. "What this study does for the first time is demonstrate a plausible explanation for these associated conditions."

The gut microbiome consists of trillions of bacteria. Rather than causing disease, most of these bacteria are friendly and aid in everything from digestion and vitamin synthesis to immune system regulation and possibly, mood stabilization.

Diet, genetics and environmental exposure all play a role in maintaining a healthy microbiome, which is critical to overall wellness, says Dr. DiBaise. Significant changes to the microbiome, like those caused by proton pump inhibitors, can put people at risk for over-colonization by such undesirable species as clostridium difficile, he says.

Proton pump inhibitors are primarily used to treat ulcers and acid reflux, and include the generic names omeprazole, pantoprazole, esomeprazole, lansoprazole, rabeprazole and dexlansoprazole.

Many epidemiological studies have linked PPIs to nutritional, metabolic and infectious disorders, despite the class of drugs' long history of safety and efficacy. Specifically, their prolonged use has been associated with iron and vitamin B12 deficiencies, hypomagnesemia, osteoporosis-related fractures, small intestinal bacterial overgrowth, and community-acquired pneumonia. The Food and Drug Administration has issued several safety communications about use of high-dose PPIs (available through prescription) and long-term use at any dose, including over-the-counter medications.

Safety implications of the study have yet to be determined, and patients should consult a qualified medical professional before changing any drug regimen, says Dr. DiBaise. "We're not saying people should stop taking their regular antacids; despite the many health risks associated with PPI use, they have an extensive track record of safety when used as directed," Dr. DiBaise says. "What we are saying is that the medical and research communities should consider these medications in the context of the patient's microbiome. This is an area that needs further study."

In patients with mild reflux symptoms, lifestyle changes may be sufficient to curb discomfort, Dr. DiBaise says. Non-pharmacological methods to control acid reflux include:

• Eat smaller portions at meals • Consume less fat • Avoid laying down for at least 2 hours after eating (avoid late-night snacks) • Wear loose fitting clothing • Elevate the head of the bed about 6 inches (this is best done by placing a block under the headboard, rather than stacking pillows) • Lose weight (as little as 5 to 10 pounds may help) • Avoid alcohol, tobacco and foods that trigger symptoms

Daily medications become necessary in those whose reflux symptoms persist and impair their quality of life despite these lifestyle modifications, says Dr. DiBaise. Whether less potent acid inhibitors like histamine H2 antagonists, cause similar changes to the microbiome is unknown.