Good or bad fiber? Inulin promotes production of type 2 inflammation, study finds

03 Nov 2022 --- Inulin, a dietary fiber frequently used in health supplements and known to have some anti-inflammatory properties, can also encourage allergy-related inflammation in the lung, gut and other body parts, according to new preclinical studies.

The researchers from the Friedman Center for Nutrition and Inflammation, Jill Roberts Institute for Inflammatory Bowel Disease and the Boyce Thompson Institute at US-based Cornell University unveiled that dietary inulin fiber changes the metabolism of specific gut bacteria, which in turn causes type 2 inflammation.

Type 2 inflammation is a particular immune response pattern. It may have advantages, such as assisting in the elimination of a parasitic infection. However, it also impacts a few illnesses, including some forms of asthma.

“There’s a lot to think about here, but, in general, these findings broaden our understanding of the relationship between diet, immunity and the normally beneficial microorganisms that constitute our microbiota and colonize our bodies,” says study co-senior author Dr. David Artis, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors professor of Immunology at Weill Cornell Medicine.

Bananas, asparagus and garlic are just a few fruits and vegetables that contain trace amounts of inulin. Additionally, it is frequently concentrated in widely accessible high-fiber nutritional supplements.

Impact on bile acids
The study found that bile acid levels were raised due to the inulin-induced growth of certain bacterial species – known as Bacteroidetes – found in mice and humans.

Inulin has been found to promote allergy-related inflammation in the lungs and gut.“We were amazed to find such a strong association between inulin supplementation and increased bile acid levels,” says Frank Schroeder, professor at the Boyce Thompson Institute’s Department of Chemistry and Chemical Biology.

“We then found that deletion of the bile acid receptor abrogates the inulin-induced inflammation, suggesting that microbiota-driven changes in bile acid metabolism underlie the effects of inulin.”

Although it plays a role in normal wound healing and is thought to have evolved in mammals primarily to protect against parasitic worm (“helminth”) infections, this type of inflammation is also believed to be the root cause of allergies, asthma and other inflammatory diseases due to its inappropriate activation.

“It could be that this inulin to type-2-inflammation pathway represents an adaptive, beneficial response to endemic helminth parasite infection, though its effects in a more industrialized, helminth-free environment are more complex and harder to predict,” says Dr. Mohammad Arifuzzaman, study researcher at the Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Department of Medicine.

Treg cell decrease, eosinophils increase
According to earlier research, inulin increases beneficial gut bacterial species’ populations, increasing regulatory T (Treg) cells, an anti-inflammatory, immune cell type.

The current study examined the effects of inulin more thoroughly. After feeding mice a high-fiber diet based on inulin for two weeks, they looked at the many variations between these mice and mice fed a diet deficient in inulin.

The inulin diet increased T cells but also caused noticeably higher levels of eosinophils, which are white blood cells, to accumulate in the gut and lungs. This was a significant difference. Eosinophilia is a classic indicator of type 2 inflammation and is frequently present in asthma and seasonal allergies.

The researchers note that although inulin was found to encourage type 2 inflammation, it does not imply that this particular type of fiber is always bad.“When we colonized germ-free mice – mice without microbiota – with one of these bacterial species and then knocked out the gene for one bacterial enzyme that promotes bile acid production, the whole pathway leading from inulin to eosinophilia and allergic inflammation was blocked,” adds Dr. Chun-Jun Guo, assistant professor of immunology in medicine at Weill Cornell Medicine.

Overall, the researchers discovered that the eosinophil response was mediated by immune cells known as group 2 innate lymphoid cells (ILC2s), which were activated by elevated blood levels of small molecules known as bile acids.

Role of type 2 inflammation
According to the researchers, the findings suggest that inulin encourages type 2 inflammation but does not imply that this particular type of fiber is always bad. They discovered that inulin made mice’s type 2 airway inflammation worse by allergens.

However, the experiments also support inulin’s previously noted ability to increase anti-inflammatory T cells, which may often outweigh some pro-inflammatory effects.

Furthermore, type 2 immune responses, which in the gut and lungs result in increased tissue-protecting mucus, are not always harmful in healthy individuals. The researchers found in their mice experiments that inulin-induced type 2 inflammation strengthens the defense against helminth worm infection.

In the future, the researchers aim to use their multi-disciplinary, multi-platform strategy to systematically investigate the immune effects of various dietary fiber types as well as a variety of other nutritional supplements in different conditions of health and disease.

Edited by Nicole Kerr