Inulin is a type of fiber found in certain plant foods and fiber supplements, and a new study by Weill Cornell Medicine researchers has found that it causes inflammation in the intestine and exacerbates inflammatory bowel disease in a preclinical model. These surprising findings could serve as a basis for developing therapeutic dietary interventions that can help alleviate symptoms and promote intestinal health.
The study has been published in Journal of Experimental Medicine and shows that inulin, which is found in foods such as garlic, leeks and Jerusalem artichoke, tupinambo or topinambur – a tuber that looks like wrinkled ginger – as well as in commonly used fiber supplements and in foods to which fiber is added, stimulates microbes in the intestine to release bile acids that increase the production of molecules that promote intestinal inflammation.
One of those proteins, IL-33, causes immune cells called group 2 innate lymphoid cells (ILC2) to activate, triggering an excessive immune response similar to an allergic reaction. This excessive immune response intensifies intestinal damage and symptoms in an animal model of inflammatory bowel disease.
Dietary fiber, including inulin, is considered essential in a healthy diet for most people. Gut microbes convert inulin and other types of dietary fiber into short-chain fatty acids that activate immune cells called regulatory T cells, which help reduce inflammation and have other beneficial effects throughout the body, which has led to a Significant increase in the use of dietary fiber as an additive, both in foods and supplements, and purified inulin or inulin-rich chicory root is usually the main source of fiber.
“Inulin is now everywhere, from clinical trials to prebiotic soft drinks,” said lead author Mohammad Arifuzzaman, a postdoctoral associate at Weill Cornell Medicine. He and his colleagues expected that inulin would also have protective effects in inflammatory bowel disease, but they found just the opposite.
Diets rich in fiber and inflammatory bowel disease
Including inulin in the diet of mice in the context of an inflammatory bowel disease model increased the production of certain bile acids by specific groups of intestinal bacteria. The increase in bile acids boosted the production of an inflammatory protein called IL-5 by ILC2s. ILC2s also failed to produce a tissue-protective protein called amphiregulin.
In response to these changes, the immune system promotes the production of immune cells called eosinophils, which further increase inflammation and tissue damage. A 2022 study by the same team of researchers showed that this rush of eosinophils may help protect against parasite infections. However, in the inflammatory bowel disease model, this chain reaction exacerbated intestinal inflammation, weight loss, and other symptoms such as diarrhea.
In patient-based translational studies, the team also analyzed human tissue, blood and stool samples from the Live Cell Bank at the Jill Roberts Institute for Inflammatory Bowel Disease Research at Weill Cornell Medicine. This analysis revealed that patients with inflammatory bowel disease, like mice fed inulin, had higher levels of bile acids in the blood and feces and excessive levels of eosinophils in the intestine compared to people without the condition.
“The present study shows that not all fibers are equal in terms of how they influence the body’s microbiota and immune system”
The results suggest that the inflammation cascade similar to that in inulin-fed mice is already activated in humans with inflammatory bowel disease, and dietary inulin intake may further aggravate the disease. These unexpected discoveries may help explain why high-fiber diets often exacerbate inflammatory bowel disease in patients and may also help scientists develop therapeutic diets to reduce symptoms and intestinal damage in patients with inflammatory bowel disease or related conditions.
New therapies are urgently needed for these increasingly common intestinal conditions. Existing biological therapies may increase the risk of developing infections or autoimmune diseases, which cause the immune system to attack the body.
“The present study shows that not all fibers are equal in how they influence the body’s microbiota and immune system,” said senior author David Artis, director of the Jill Roberts Institute for Inflammatory Bowel Disease Research and director from the Friedman Center for Nutrition and Inflammation at Weill Cornell Medicine. “These findings could have broader implications for delivering precision nutrition to individual patients to promote their overall health based on their unique symptoms, microbiota composition, and dietary needs,” he concludes.
