Return of the Farm Effect

By Dr. Paul Ehrlich

Ever since the dawn of the hygiene hypothesis, allergists have wondered whether hanging around the barn could help stave off the development of allergies and asthma. This website has certainly covered the observed phenomenon ever since my former student Dr. Mark Holbreich published his famous “Amish Study.” Now some new research from Europe draws us closer to understanding the mechanisms for this protection. As an article in Science puts it, “Bits of bacteria found in farm dust trigger an inflammatory response in the animals’ lungs that later protects them from asthma. An enzyme involved in this defense is sometimes disabled in people with asthma, suggesting that treatments inspired by this molecule could ward off the condition in people.”

The full article, which is signed by Dr. Erika Von Mutius, among others, who is considered the originator of the hygiene hypothesis, recounts a mouse experiment that approximates the chronic low-dose exposure to an endotoxin (bacterial lipopolysaccharide, that makes up the outer layer of the cell membrane of bacteria)

, which is plentiful in a farm environment. They showed that mice were protected from developing house dust mite (HDM)–induced asthma. “Endotoxin reduced epithelial cell cytokines that activate dendritic cells (DCs), thus suppressing type 2 immunity to HDMs. Loss of the ubiquitin-modifying enzyme A20 in lung epithelium abolished the protective effect.” This confirmed research published more than a decade ago in the New England Journal of Medicine, although that paper also spoke of the dangers of too much endotoxin and the danger of autoimmune disease.

The current paper also validated the mouse findings in human cells.

This is very exciting. It strengthens the current theory that allergies are caused by disturbances in the innate and acquired immune systems. Early exposure to these endotoxins seems to present the immune system with the right challenge at the right time, strengthening the Th1 (T helper cell) immune function. Without this nudge, the immature immune system leans towards the Th2 side, which is allergy prone. This suggests that it may be possible to protect future generations without having to relocate pregnant mothers and newborns to the countryside.

It won’t happen quickly. As I have pointed out previously, not all farms are the same. For example, women from Hutterite farms, which share many qualities with the Amish, have higher rates of asthma than the men. I imagine that non-Amish farm children play Xbox these days, and even Amish children get asthma. There are many reasons why a low-dose endotoxin treatment will have mixed real-world results. Still the idea that heroic research may allow us to restore natural balance to an unnatural environment is very exciting to me, and I look forward to more.

Photo from wikipedia commons