Research points to new ways to treat inflammatory bowel diseases

| Written by jmoore
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A new paper in Nature co-authored by SBP’s Randal Kaufman, Ph.D., reveals how briefly reducing dietary amino acids could help patients with inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. The research shows for the first time that a specific amino acid sensor controls gut inflammation.

These results, generated in the laboratory of Bali Pulendran, Ph.D., of Emory University, could also lead to new drugs for IBD, which are sorely needed—currently available drugs don’t work for many patients.

What was known before this study

The amino acid sensor studied, GCN2, is one of four sensors that activate the integrated stress response (ISR) (the other sensors respond to different types of cellular stress). Activation of the ISR alters gene expression in ways that help cells survive: facilitating efficient utilization of nutrients, combating oxidative stress, and repairing DNA damage. While previous research had shown that the ISR helps limit gut inflammation, this is the first to implicate GCN2.

Significance

The findings “highlight the capacity of the immune system to sense and adapt to environmental changes, such as nutritional starvation, that cause cellular stress,” said Kaufman.

“This response may have evolved as a negative feedback mechanism to limit inflammation. This mechanism ensures that sufficient building blocks are available for the tissue regeneration required to repair the damage caused by inflammation and prevents the immune response from getting out of control.”

Implications for IBD

While GCN2’s anti-inflammatory activity can be triggered by a low-amino acid diet, reducing protein intake is not a feasible long-term treatment for IBD because it would generally impair the immune system. If human studies confirm that GCN2 is also protective in human disease, drugs that target GCN2 or later steps in the ISR could be developed to treat IBD.

Next steps

“We plan to investigate whether this pathway is involved in regulating other types of inflammation. If it is, this discovery could be important for treating other diseases like rheumatoid arthritis or multiple sclerosis,” Kaufman added.

The paper is available online here.

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