Using drugs or diet to restore the body's natural defenses to gut infections may offer a new way to treat currently incurable bowel diseases such as Crohn's disease, European scientists said on Monday.
Researchers led by scientists from the Pasteur Institute in Lille, France, found that having low levels of a protein called PPAR-gamma, which regulates defenses that kill bacteria in the gut, may make patients less able to fight off gut infections — so boosting PPAR-gamma could help protect against such diseases.
Mathias Chamaillard, who led the study, said in a telephone interview that foods or diets containing conjugated linoleic acid (CLA) can boost PPAR-gamma activit and have been shown to improve colitis and colitis-associated cancer.
CLA is primarily found in milk and meat products, and is also available as a supplement.
Chamaillard said the results showed that drugs already used for other diseases could prove effective in Crohn's disease.
For example, GlaxoSmithKline's diabetes drug Avandia, known generically as rosiglitazone, has been shown to restore gut defenses through PPAR-gamma activation, he said, and Takeda Pharmaceutical's Actos, or pioglitazone, another PPAR drug used in diabetes, acts in the same way.
Inflammatory bowel conditions such as Crohn's disease and ulcerative colitis affect around 0.5 percent of the population in developed nations and are notoriously difficult to treat.
Treatments include a group of injectable drugs that block an inflammatory protein called tumor necrosis factor (TNF) such as Johnson & Johnson's Remicade, Abbott's Humira, and UCB's Cimzia. Chamaillard said not all patients respond to these, and others find they stop being effective over time.
The European team, whose work was published in the Proceedings of the National Academy of Sciences (PNAS) journal, used mice engineered to be low in PPAR-gamma and found they were less able to fight off bacterial infection in the colon compared to normal mice.
Samples taken from the colons of humans diagnosed with Crohn's disease also show reduced levels of the antimicrobial peptides, or defenses, regulated by the PPAR-gamma protein, they wrote.
"In the short term, managing the disease is what we are looking at, but it may also be that in the future we could develop a way of stopping it," Chamaillard said.
But he added that curing Crohn's disease would mean being able to identify those at highest risk before they contracted it, and then being able to boost PPAR gamma-related defenses to ward it off — both areas that would need more research.
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