Dietary fiber promote inflammation in gut: Research

WASHINGTON: Researchers have discovered that a dietary fiber known as inulin, which is used in health supplements and has some anti-inflammatory qualities, can also encourage an allergy-related kind of inflammation in the gut and lungs as well as other parts of the body.

Researchers from the Boyce Thompson Institute on Cornell University's Ithaca campus, the Friedman Center for Nutrition and Inflammation, the Jill Roberts Institute for Inflammatory Bowel Disease, and Weill Cornell Medicine published their findings in the journal Nature.

According to the study, dietary inulin fibre modifies the metabolism of specific gut bacteria, which in turn causes type 2 inflammation in the lungs and gut. 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 thought to be the root cause of allergies, asthma, and other inflammatory diseases due to its inappropriate activation.

"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," said 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.

Participants from Weill Cornell Medicine in New York City, Cornell University's Ithaca campus, and other institutions with expertise in bacterial genetics, biochemistry, and immunology represent the Friedman Center's commitment to highly interdisciplinary research collaboration.

Dr. Frank Schroeder, professor at the Boyce Thompson Institute and the Department of Chemistry and Chemical Biology in the College of Arts and Sciences on Cornell's Ithaca campus, and Dr. Chun-Jun Guo, assistant professor of immunology in medicine at Weill Cornell Medicine, collaborated with the Artis laboratory to gain a thorough understanding of how an essential dietary component affects the microbiome and the immune response.

The study's first author is Dr. Mohammad Arifuzzaman, a postdoctoral researcher in the Artis laboratory.Dr. Artis is also director of the Jill Roberts Institute for Inflammatory Bowel Disease at Weill Cornell Medicine.

Bananas, asparagus, and garlic are just a few of the many fruits and vegetables that contain trace levels of inulin. Additionally, it is typically concentrated in widely accessible high-fiber nutritional supplements. According to earlier research, inulin increases populations of helpful gut bacterial species, which in turn increases numbers of regulatory T (Treg) cells, an anti-inflammatory immune cell type.

The effects of inulin were more thoroughly explored in this recent study. After feeding mice a high-fiber diet based on inulin for two weeks, they examined the many variations between these animals and mice that had been fed a diet deficient in inulin. The inulin diet increased Treg cells, but it also caused noticeably larger amounts 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 seen in asthma and seasonal allergies.

Finally, the researchers discovered that increased blood levels of bile acids activated immune cells known as group 2 innate lymphoid cells (ILC2s), which were responsible for the eosinophil response. The bacterial species known as Bacteroidetes, which are prevalent in both mice and people, grew more quickly when inulin was present, and they have an enzyme that can metabolize bile acids, which is why the levels of bile acid were higher.

"We were amazed to find such a strong association between inulin supplementation and increased bile acid levels," Dr. Schroeder said. "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."

"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," Dr. Guo said. The finding that inulin promotes type 2 inflammation does not mean that this type of fiber is always "bad," the researchers said. They found that inulin did worsen allergen-induced type 2 airway inflammation in mice. But the experiments also confirmed inulin's previously reported effect at boosting anti-inflammatory Treg cells, which may in many cases, outweigh some pro-inflammatory impact.

Moreover, a type 2 immune response, which in the gut and lungs involves an increased production of tissue-protecting mucus, is not necessarily harmful in healthy people-indeed, the researchers found in their mouse experiments that the inulin-induced type 2 inflammation enhances the defense against helminth infection.

"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," said Dr. Arifuzzaman.

Now, the scientists want to employ their multi-disciplinary, multi-platform strategy to comprehensively investigate the immunological effects of various dietary fibre types as well as a variety of additional dietary supplements in various conditions of health and disease.