Nature: A common dietary fiber that promotes an allergy-like immune response

A preclinical study showed that a dietary fiber called inulin, commonly used in health supplements, is known to have some anti-inflammatory properties, but it also promotes an allergy-related inflammation in the lungs, intestines and other parts of the body, according to researchers
from the Friedman Center for Nutrition and Inflammation at Weill Cornell Medical School and the Gil Roberts Institute for Inflammatory Bowel Disease and the Boyce Thompson Institute at Cornell University's Ithaca campus.

Research published Nov.
2 in Nature found that dietary inulin fiber alters the metabolism of certain gut bacteria, triggering what scientists call type 2 inflammation
of the gut and lungs.
This type of inflammation is thought to have evolved in mammals, primarily to ward off parasitic infections and as part of normal wound healing, although its improper activation underlies
allergies, asthma, and other inflammatory diseases.

"There's a lot to think about here, but taken together, the findings broaden our understanding of the relationship between diet, immunity, and the generally beneficial microbes that make up our microbiome and settle on our bodies," said
David Artis, Ph.
D.
, senior co-author of the study, director of the Friedman Center for Nutrition and Inflammation and the Michael Coles Professor of Immunology at Weill Cornell Medical College.

Small amounts of inulin are found in a variety of fruits and vegetables, including bananas, asparagus, and garlic
.
It is also often concentrated in
common high-fiber dietary supplements.
Previous studies have found that inulin increases the number of beneficial gut bacterial species, which in turn raises levels
of anti-inflammatory immune cells called regulatory T (Treg) cells.

In the new study, the researchers examined the effects
of inulin more comprehensively.
They fed the mice an inulin-based, high-fiber diet for two weeks, and then analyzed many of the differences
between these mice and those fed inulin-free food.
One major difference is the inulin diet, which, while increasing Treg cells, also induces significantly elevated
levels of white blood cells called eosinophils in the gut and lungs.
High levels of eosinophils are classic signs of type 2 inflammation, usually seen in seasonal allergies and asthma
.

Ultimately, the researchers found that the eosinophil response is mediated by a type of immune cell called group 2 innate lymphoid cells (ILC2s), which is activated
by elevated levels of small molecules called bile acids in the blood.
The elevated level of bile acids is due to inulin-induced growth of a certain bacterial species — a bacterium known as the phylum Desmycetes, found in both mice and humans — with bile acid-metabolizing enzymes
.

"We were surprised to find such a strong link
between inulin supplementation and elevated bile acid levels.
We then found that the loss of bile acid receptors eliminated inulin-induced inflammation, suggesting that changes in bile acid metabolism driven by the microbiota underlie
inulin's action.
When we colonized germ-free mice (germ-free colonies) with one of these bacteria and then knocked out a gene that promotes chooleic acid production, the entire pathway from inulin to eosinophilia and allergic inflammation was blocked," the researchers said
.

The researchers say the discovery that inulin promotes type 2 inflammation doesn't mean this type of fiber is always "bad.
"
They found that inulin did exacerbate allergen-induced inflammation
of the mouse type 2 airways.
But experiments have also confirmed inulin's previously reported role in promoting anti-inflammatory Treg cells, which in many cases may outweigh some pro-inflammatory effects
.
In addition, the type 2 immune response (an increase in mucus involved in protective tissues in the gut and lungs) is not necessarily harmful to healthy people — in fact, the researchers found in mouse experiments that inulin-induced type 2 inflammation boosts defenses against helminth infections
.

Dr Arifuzzaman said: "It is possible that this pathway from inulin to type 2 inflammation represents an adaptive, beneficial response to endemic parasitic infections, although its effects are more complex and less predictable
in a more industrialized, parasite-free environment.
"

The researchers now plan to use their multidisciplinary, multi-platform approach to systematically study the immune effects
of different types of dietary fiber, as well as a range of other dietary supplements, in different health and disease states.

Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation