Thursday, September 17, 2015

Dirt’s Partner in Protecting Children from Asthma

photo by Scott Bauer from USDA

For more than a quarter of a century scientists have observed that children growing up on a dairy farm have a lower incidence of allergy, hay fever and asthma and other respiratory diseases than other children. At least a dozen observational studies aimed at uncovering the underlying cause of the increased incidence of asthma in children have confirmed this protective effect. This observation has produced the idea known as the hygiene hypothesis, that our modern obsession with cleanliness and widespread use of antibiotics and antibacterial soaps has purged our homes of microorganisms that once taught a child’s developing immune system not to overreact to foreign substances.

Endotoxins are part of the outer membrane of bacteria and are shed into the environment after bacteria die. Endotoxins, potent stimulators of the immune system, are ubiquitous. Though exposure to dirt containing endotoxins is probably only one explanation for the protective effect of growing up on a dairy farm, the correlation has been confirmed. A 2013 paper by Barnig et al “Indoor dust and air concentrations of endotoxin in urban and rural environments” that analyzed endotoxins in farmhouses and non-farmhouses found that endotoxin levels were significantly higher in floor and mattress dust in farmhouses compared to other rural and urban homes. Lack of ventilation and direct entry into the house were found to correlate with an increase in dust endotoxin levels. However, the scientists in that study found no difference between endotoxin concentrations in the air of urban and rural houses, and airborne endotoxin levels did not correlate to dust levels.

It was assumed that the dust containing the endotoxins acted directly to train the immune system’s T cells. However, in a new paper published September 4th 2015 in Science Magazine, “Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells,“ scientists from Gent University and Flanders Institute in Belgium have found another mechanism by which the endotoxins provide protection. A20 is an enzyme made by the epithelial cells in the respiratory tract and lungs. In laboratory studies using mice the scientists showed that chronic exposure to dust containing elevated levels of endotoxins provided protection from developing asthma. The experiments provided evidence that environmental protective factors can work by suppressing the activation of epithelial cell cytokines that activate dendritic cells (inflammatory molecules) through the induction of the ubiquitin–modifying enzyme A20.

In mice that were specially engineered to lack the gene for A20 in their lung epithelial cells, endotoxin exposure did not provide protection from asthma. The scientists also tested the response of human bronchial cells harvested from healthy people and people with asthma. The scientists found that exposure to endotoxins lowered the levels of the inflammatory molecules in the healthy cells. Despite endotoxin exposure the levels of inflammatory molecules did not decrease as much in cells from people with asthma and that those cells also made less of the enzyme A20.

This newly discovered mechanism for protection from asthma is unlikely to be the only pathway of protection for farm children from allergy, hay fever and asthma and other respiratory diseases. Within the gut, colonizing microbial induct the express of A20 shortly after birth to dampen inflammation to commensal bacteria. In a 2013 study in Poland it was found that early-life exposure to unpasteurized milk appears to protect against asthma, and related conditions, independently of place of residence and farming status, and in both children and adults. What we are also learning is how complicated an organism we are and important commensal bacteria are.

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