Proton Pump Inhibitors Cause Small Intestine Bacterial Imbalance

Background & Aims
Proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used classes of drugs, with the former frequently coprescribed to reduce gastroduodenal injury caused by the latter. However, suppression of gastric acid secretion by PPIs is unlikely to provide any protection against the damage caused by NSAIDs in the more distal small intestine.

Methods
Rats were treated with antisecretory doses of omeprazole or lanzoprazole for 9 days, with concomitant treatment with anti-inflammatory doses of naproxen or celecoxib on the final 4 days. Small intestinal damage was blindly scored, and changes in hematocrit were measured. Changes in small intestinal microflora were evaluated by denaturing gradient gel electrophoresis and reverse-transcription polymerase chain reaction.

Results
Both PPIs significantly exacerbated naproxen- and celecoxib-induced intestinal ulceration and bleeding in the rat. Omeprazole treatment did not result in mucosal injury or inflammation; however, there were marked shifts in numbers and types of enteric bacteria, including a significant reduction (80%) of jejunal Actinobacteria and Bifidobacteria spp. Restoration of small intestinal Actinobacteria numbers through administration of selected (Bifidobacteria enriched) commensal bacteria during treatment with omeprazole and naproxen prevented intestinal ulceration/bleeding. Colonization of germ-free mice with jejunal bacteria from PPI-treated rats increased the severity of NSAID-induced intestinal injury, as compared with mice colonized with bacteria from vehicle-treated rats.

Conclusions
PPIs exacerbate NSAID-induced intestinal damage at least in part because of significant shifts in enteric microbial populations. Prevention or reversal of this dysbiosis may be a viable option for reducing the incidence and severity of NSAID enteropathy.

From press release:

Patients often take drugs to lower stomach acid and reduce the chances they will develop ulcers from taking their anti-inflammatory drugs for conditions such as arthritis, but the combination may be causing major problems for their small intestines, McMaster researchers have found.

A team from the Farncombe Family Digestive Health Research Institute has found those stomach acid-reducing drugs, known as proton pump inhibitors, may actually be aggravating damage in the small intestine caused by the nonsteroidal anti-inflammatory drugs, also known as NSAIDs.

In a study published in the medical journal Gastroenterology, principal investigator John Wallace says the extent of the hard-to-detect damage caused to the small intestine has only recently been discovered through use of small video cameras swallowed like pills.

"Suppressing acid secretion is effective for protecting the stomach from damage caused by NSAIDs, but these drugs appear to be shifting the damage from the stomach to the small intestine, where the ulcers may be more dangerous and more difficult to treat," said Wallace. He is director of the Farncombe institute and professor of medicine of the Michael G. DeGroote School of Medicine at McMaster.

He added that the use of probiotics is being investigated as a potential cure for the small intestine damage.

The study was funded by the Canadian Institutes of Health Research (CIHR) and a CIHR/Canadian Association of Gastroenterology Fellowship.