Rise in Allergies Linked to War on Bacteria
- By Ars Technica
- March 28, 2012 |
By Diana Gitig, Ars Technica
“Allergic diseases have reached pandemic levels,” begins David Artis’s new paper in Nature Medicine. Artis goes on to say that, while everyone knows allergies are caused by a combination of factors involving both nature and nurture, that knowledge doesn’t help us identify what is culpable — it is not at all clear exactly what is involved, or how the relevant players promote allergic responses.
There is some evidence that one of the causes lies within our guts. Epidemiological studies have linked changes in the species present in commensal bacteria — the trillions of microorganisms that reside in our colon — to the development of allergic diseases. (Typically, somewhere between 1,000 and 15,000 different bacterial species inhabit our guts.) And immunologists know that signaling molecules produced by some immune cells mediate allergic inflammation. Animal studies have provided the link between these two, showing that commensal bacteria promote allergic inflammation. But these researchers wanted to know more about how.
To figure it out, Artis and his colleagues at Penn’s School of Veterinary Medicine treated mice with a broad range of oral antibiotics to diminish or deplete their commensal bacteria and then examined different immunological parameters. They used a combination of five different antibiotics, ranging from ampicillin, which is fairly run of the mill, to vancomycin, which is kind of a nasty one.
They found that mice treated with antibiotics had elevated levels of antibodies known to be important in allergies and asthma (IgE class antibodies). The elevated antibodies in turn increased the levels of basophils, immune cells that play a role in inflammation, both allergic and otherwise.
This connection doesn’t only apply to mice but also to humans who have high levels of IgE for genetic reasons. People with genetically elevated levels of IgE are hypersusceptible to eczema and infections, and antibodies that neutralize IgE are used to treat asthma.
The antibiotic treatments and IgE did not act by promoting the survival of mature basophils, but rather by promoting the proliferation of basophil precursor cells in the bone marrow. Commensal bacteria limit this proliferative capacity.
That discovery is the real insight contributed by this paper. It has been well known for some time that IgE mediates allergies. But no one knew that bacteria living in the gut may use it to check the growth of immune precursor cells in the bone marrow. The finding might have wide-ranging implications and help us make sense of other chronic inflammatory disease states that have also been associated with changes in this bacterial populations. Commensal bacteria might impact these other inflammatory conditions — including cancer, infection, and autoimmune disorders — through this mechanism, as well.
Experts have puzzled over the enormous explosion of asthma and allergies in recent years, and been unable to pinpoint the cause. This paper suggests that perhaps the overuse of antibacterial products could be to blame.
Image: Janice Haney Carr/CDC
Citation: “Commensal bacteria–derived signals regulate basophil hematopoiesis and allergic inflammation.” David A Hill, Mark C Siracusa, Michael C Abt, Brian S Kim, Dmytro Kobuley, Masato Kubo, Taku Kambayashi, David F LaRosa, Ellen D Renner, Jordan S Orange, Frederic D Bushman and David Artis. Nature Medicine, published online March 25, 2012. DOI: 10.1038/nm.2657