New Insight into How an Old IBD Drug Works


In a study recently published in Cell Reports Medicine, a team of researchers lead by senior author Dr. Randy Longman, Director of the Jill Roberts Center for IBD and Associate Professor of Medicine at Weill Cornell Medicine in the Division of Gastroenterology & Hepatology, examined IBD-SpA patients treated with sulfasalazine and found that the presence of the gut bacterium Faecalibacterium prausnitzii was a key factor enabling successful treatment responses. They determined that sulfasalazine works by upregulating this bacterium’s production of butyrate, a fatty acid molecule with anti-inflammatory properties.

“These findings offer a way to identify IBD-SpA patients who are likely to respond to sulfasalazine therapy, and also suggest new therapeutic approaches,” Dr. Longman said. The co-first authors were Dr. Svetlana Lima and Dr. Silvia Pires, both postdoctoral research associates in the Longman laboratory during the study. 

It is estimated that more than two million Americans have IBD, which comprises two distinct disorders, ulcerative colitis and Crohn’s disease. A variety of treatments are available, but their effectiveness is limited, essentially because scientists don’t fully understand the immunological processes that trigger and sustain IBD.

IBD frequently coexists with SpA, and sulfasalazine reduces or eliminates symptoms of both conditions in many of these patients. Prior studies have suggested that it works via the gut microbiome, though the precise mechanism has never been clear.

The study overall suggests that a clinical test for the presence of key bacteria could someday be used to identify patients who are more likely to benefit from sulfasalazine treatment, Dr. Longman said. He added that this approach may be applicable not just to combined IBD-SpA but to either condition separately.

The results also point to the possibility of therapies that would add F. prausnitzii to the gastrointestinal tracts of IBD and SpA patients, to boost responsivity to sulfasalazine. Butyrate oral supplements are already popular, and gastroenterologists commonly give butyrate enemas to patients, yet these are only partially effective. Dr. Longman suspects that bacteria living in the gut lining are best placed to deliver this beneficial molecule.

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