Jakob, Dahl and co-workers, as well as researchers from the U-M College of Pharmacy and U-M Medical School, showed that mesalamine targets the production of polyphosphate and caused bacteria to behave as if they lacked this vital substance.”We now know that mesalamine is making certain bacteria more sensitive to conditions they would encounter in the inflamed gut, which might explain how mesalamine treatment improves the gut microbiome,” said Jakob, the study’s lead investigator.The researchers, who also include Jakob’s former postdoctoral student Michael Gray, screened thousands of molecules to find which of the molecules was stopping the bacteria from producing polyphosphate. This test turned up mesalamine. Spearheaded by professor Duxin Sun in the College of Pharmacy, the researchers then gave mesalamine to a group of healthy study participants.

After a period of time—up to seven hours after treatment—the researchers took samples from the participants’ gastrointestinal tracts. In the samples that did not show mesalamine, the study participants showed stable levels of polyphosphate. But that changed once mesalamine became detectable.”The moment we could detect mesalamine, the polyphosphate levels dropped dramatically,” Dahl said.The next step for the researchers will be to administer mesalamine to patients with colitis to study how their microbiome changes and to search for other uses for mesalamine.”We do not want to say that this is the only mechanism by which mesalamine works,” Jakob said. “But it is clear that mesalamine has an effect on microbes and targets a very specific defense system in those bacteria.”

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