For gastrointestinal diseases, dogged research offers advances in science, care

When Mark Pimentel, MD, first suggested a decade ago that bacteria play a key role in causing irritable bowel syndrome, the scientific community reacted with skepticism. Conventional wisdom then decreed this disease had its roots in the brain not the gut as IBS sufferers generally were thought to have psychological issues.

Today, Pimentel possesses an "archive" shelf in his office, stuffed with scores of articles challenging his theory, including a National Enquirer story on his research that ran next to a piece on a "miracle" weeping statue.

The 44-year-old Cedars-Sinai researcher continues to vanquish doubters as he amasses scientific evidence to show the role of bacteria in IBS, a chronic ailment affecting an estimated 30 million Americans. He also has developed the first treatment to offer patients, with antibiotics, a long-lasting easing of their symptoms, as shown in research published in the New England Journal of Medicine.

What's IBS?

Irritable bowel syndrome is the most common gastrointestinal disorder in the United States, affecting about 30 million people. Traditionally, patients with IBS have been described as "constipation predominant," "diarrhea predominant," or an alternating pattern of constipation and diarrhea. Other common symptoms include abdominal pain or cramps, excess gas or bloating, and visible abdominal distension.

Though his explanation for IBS has gone from medical outlier to orthodoxy, Pimentel still prints his research posters for professional conferences in white text on a black background – a tongue-in-cheek tribute to his onetime status as the "black sheep" among GI disease researchers. Pimentel does take seriously research that may provide advances in caring for those with a disease that drastically affects their quality of life. His dogged scientific labors, he says, weren't about being proven right.

"My patients were getting better," said Pimentel, director of the GI Motility Program at Cedars-Sinai, part of the gastrointestinal team that has consistently been ranked among the nation's best. "After years of not having many options, we found antibiotic treatments were working. And now, not only are patients getting better, they're staying better after they stop the medication. That means we're attacking the cause. But we had to prove this in a systematic and scientific fashion."

His long pursuit of IBS' cause and therapies for it has laid the groundwork for other research examining the crucial role of bacteria in the intestine and its overall effect on health, including potential links to obesity. His work also has uncovered specific bacteria that may be key to the disease, as well as methods to more accurately diagnose it.

Leadership in research, therapies

Pimentel is just one of several Cedars-Sinai researchers who have been leaders in explaining the causes and mechanisms behind diseases, especially those involving the gut. Stephan R. Targan, MD, at left, director of the Inflammatory Bowel Immunobiology Institute and Feintech Family Chair in Inflammatory Bowel Disease, helped shift scientists' understanding of IBD so they see it now not as a single disease but many; he did this, in part, by showing that there were different disease mechanisms in different patient groups that could be potentially defined by immunologic responses and genetic variations.

Dermot McGovern, MD, PhD, FRCP, recently named the Joshua L. And Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics (the world's first endowed chair in this discipline), serves as director of Translational Medicine for the Inflammatory Bowel Disease Center and Immunobiology Research Institute. He is internationally recognized for his expertise in the genetics of Crohn's Disease and ulcerative colitis. He has developed multidimensional models for predicting disease severity and response to therapy in IBD that serve as an important step toward personalized treatment for the disease.

Pimentel, who underscores the importance of his team and colleagues in his research, says Cedars-Sinai's special mix as both a world-class research institution and a major medical center greatly benefited his investigations, which he notes received a quiet but robust support – no matter the critics outside.

"Research is the lifeblood of medicine," said Shlomo Melmed, MD, Cedars-Sinai senior vice president of academic affairs, dean of the medical faculty and Helene A. and Philip E. Hixon Chair in Investigative Medicine. Melmed is world-renowned in his field for his research that has deepened the understanding of and improved the treatment of pituitary tumors. "It is a crucial part of our mission to provide the best care available to patients today and to uncover the innovative medical breakthroughs that will heal patients in the future."

Because IBS' cause had been elusive, treatments for it had focused on relieving its symptoms with medications to slow or speed up the digestive process. Earlier research by Pimentel and colleagues documents a link between bloating, the most common symptom, and bacterial fermentation in the gut related to small intestine bacterial overgrowth, or SIBO.

Now Pimentel and other Cedars-Sinai researchers are examining this bacterial overgrowth and its link to another prevalent disease: obesity. A study examining the role of methane-producing bacteria in obesity found that those patients who tested positive for the bugs had a significantly higher body mass index, even compared to other patients whose BMI was in the obese range.

"It's exciting to be part of research that could help millions of people dramatically improve their quality of life," Pimentel said.

Antibiotics and IBS

The antibiotic therapy developed by Pimentel and his colleagues is the first drug treatment to provide patients with long-lasting relief of their symptoms – even after stopping the medication. Recent research presented by Pimentel and his colleagues also has shown that it is among the safest treatments available for IBS.

In two 600-plus patient double-blind trials, IBS patients with mild to moderate diarrhea and bloating were randomly assigned to take a 550 milligram dose of rifaximin or placebo three times daily for two weeks. Rifaximin is a minimally absorbed antibiotic that stays in the gut. Study participants were followed for 10 weeks more after taking the drug; 40 percent of patients who took rifaximin reported significant relief from bloating, abdominal pain and loose or watery stools – relief that was sustained for weeks after stopping the antibiotic.

This therapy was demonstrated as effective for IBS patients without constipation. Pimentel, whose medical training traces to the University of Manitoba in Winnipeg, Canada, is studying the effectiveness of antibiotic treatments for patients with the "constipation-predominant" form of the condition.