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Common dietary fiber promotes allergy-like immune responses



Inulin, a sort of dietary fiber commonly utilized in health supplements and known to have certain anti-inflammatory properties, may also promote an allergy-related sort of inflammation within the lung and gut, and other parts of the body, in accordance with a preclinical study from researchers within the Friedman Center for Nutrition and Inflammation and Jill Roberts Institute for Inflammatory Bowel Disease at Weill Cornell Medicine and within the Boyce Thompson Institute on Cornell’s Ithaca campus.

The study, published Nov. 2 in Nature, found that dietary inulin fiber alters the metabolism of certain gut bacteria, which in turn triggers what scientists call type 2 inflammation within the gut and lungs. Such a inflammation is believed to have evolved in mammals chiefly to defend against parasitic worm (“helminth”) infections, and can also be a part of normal wound healing, although its inappropriate activation underlies allergies, asthma and other inflammatory diseases.

“There’s loads to take into consideration here, but, normally, these findings broaden our understanding of the connection between eating regimen, immunity and the normally helpful microorganisms that constitute our microbiota and colonize our bodies,” said study co-senior creator David Artis, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology at Weill Cornell Medicine.

The study’s scientific participants reflect the Friedman Center’s highly cross-collaborative research mission, drawing on expertise in bacterial genetics, biochemistry and immunology across Weill Cornell Medicine in Latest York City and Cornell’s Ithaca campus. Chun-Jun Guo, assistant professor of immunology in medicine at Weill Cornell Medicine, and Frank Schroeder, professor on the Boyce Thompson Institute and within the Department of Chemistry and Chemical Biology within the College of Arts and Sciences, teamed up with the Artis laboratory to achieve an in depth understanding of how a crucial dietary component affects the microbiome and the immune response.

The study’s first creator is Mohammad Arifuzzaman, a postdoctoral researcher within the Artis laboratory. Artis can also be director of the Jill Roberts Institute for Inflammatory Bowel Disease at Weill Cornell Medicine.

Small amounts of inulin are present in a wide selection of vegetables and fruit, including bananas, asparagus and garlic. It is usually regularly concentrated in commonly available high-fiber dietary supplements. Previous studies have found that inulin boosts populations of helpful gut bacterial species, which in turn boost levels of anti-inflammatory immune cells called regulatory T (Treg) cells.

On this latest study, the researchers examined inulin’s effects more comprehensively. They gave mice an inulin-based, high-fiber eating regimen for 2 weeks, after which analyzed the numerous differences between these mice and mice that had been fed a eating regimen lacking inulin. A serious difference was that the inulin eating regimen, while increasing Treg cells, also induced markedly higher levels of white blood cells called eosinophils within the gut and lungs. A high level of eosinophils is a classic sign of type 2 inflammation and is usually seen within the setting of seasonal allergies and asthma.

Ultimately the researchers found that the eosinophil response was mediated by immune cells called group 2 innate lymphoid cells (ILC2s), which were activated by elevated levels of bile acids – small molecules within the blood. The bile acid levels were elevated attributable to the inulin-induced growth of Bacteroidetes, a bacterial species present in each mice and humans, which have a bile acid-metabolizing enzyme.

“We were amazed to seek out such a powerful association between inulin supplementation and increased bile acid levels,” 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 results of inulin.”

“After we colonized germ-free mice (mice without microbiota) with considered one of these bacterial species, after which knocked out the gene for one bacterial enzyme that promotes bile acid production, the entire pathway leading from inulin to eosinophilia and allergic inflammation was blocked,” Guo said.

The finding that inulin promotes type 2 inflammation doesn’t mean that this kind of fiber is all the time “bad,” the researchers said. They found that inulin did worsen allergen-induced type 2 airway inflammation in mice. However the experiments also confirmed inulin’s previously reported effect at boosting anti-inflammatory Treg cells, which can in lots of cases outweigh some pro-inflammatory impact. Furthermore, a sort 2 immune response, which within the gut and lungs involves an increased production of tissue-protecting mucus, just isn’t necessarily harmful in healthy people – indeed, the researchers present in their mouse experiments that the inulin-induced type 2 inflammation enhances the defense against helminth infection.

“It may very well be that this inulin to type-2-inflammation pathway represents an adaptive, helpful response to endemic helminth parasite infection, though its effects in a more industrialized, helminth-free environment are more complex and harder to predict,” Arifuzzaman said.

The researchers now plan to make use of their multidisciplinary, multiplatform approach to review systematically the immune effects of the differing types of dietary fiber in addition to a spread of other dietary supplements in several states of health and disease.

This work was supported partially by the National Institutes of Health, the AGA Research Foundation, the WCM-RAPP Initiative, the W. M. Keck Foundation, the Howard Hughes Medical Institute, the LEO Foundation, CURE for IBD, the Jill Roberts Institute for Research in IBD, the Sanders Family Foundation and the Rosanne H. Silbermann Foundation.

Jim Schnabel is a contract author for Weill Cornell Medicine.

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