21st century medicine | Being raised on a farm affects regulation of immune system and reduces immunological responses
LINDELL BEACH, B.C. — Many rural people believe there is a connection between farm living and health, but now there is hard science to back it up.
For the first time, a new study has shown that being raised on a farm directly affects the regulation of the immune system and reduces the immunological responses to proteins in food.
“There is a great deal of self-diagnosis, especially in relation to food allergies, most of which are inaccurate,” said Dr. Marie Lewis, a research associate in infection and immunity at the University of Bristol’s School of Veterinary Sciences in the United Kingdom.
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“However, there is unequivocal evidence that the incidence of all immunological and metabolic diseases are increasing and are a major challenge for 21st century medicine.”
The need to understand the complex correlation between immune drivers and the environment is becoming a top priority.
“In the intestine, immune responses against ‘harmless’ antigens are associated with autoimmunity, inflammatory disease and allergy, and there is increasing evidence that such responses are controlled by regulatory T-lymphocytes,” Lewis wrote in a research paper that was recently published in Pediatric Allergy and Immunology.
“There is clear indication that expansion of a competent immune system in neonates depends on the composition of the intestinal microbiota and therefore exposure to environmental microbes. However, the mechanisms linking early-life environment to later development of allergy are only just starting to be clarified.”
The research paper, “Direct experimental evidence that early-life farm environment influences regulation of immune responses,” showed that children who spend their early years in a complex farm environment increased their number of regulatory T-lymphocytes, the immune cells that drive and limit immune responses.
“Many large-scale epidemiological studies have suggested that growing up on a farm is linked to a reduced likelihood of developing allergic disease,” said Lewis, who headed the research team and was lead author of the paper.
“However, until now it has not been possible to demonstrate direct cause and effect: does the farm environment actively protect against allergies, or are allergy-prone families unlikely to live on farms?”
Enter piglets.
Pigs are valuable models for humans with similarities in digestive physiology, immunology, metabolism and genetics, and research using pigs can be reliably translated to underscore the human condition. They can also get allergies that are caused by the same mechanism as in humans., making them the ideal farm animal to conduct environmental exposure tests.
In the study, some piglets were nursed by their sows on a farm while their siblings, from one day of age onward, were reared in an isolator unit under extremely hygienic conditions and fed formula milk, reflecting the environmental extremes under which human babies can be raised.
“Six piglets from six sows were left on the farm while a sibling from each litter was brought into the isolator,” said Lewis.
“An additional six adult pigs were used for comparison purposes. The sows were all from one farm and since we used siblings in the isolator it was only necessary to look at one farm. If we had used unrelated piglets, we would have had to use a series of different farms.”
She said the farm piglets were reared in a barn in a farrowing unit with slatted flooring so that droppings fell through, although some messy residue remained. However, the isolator piglets were bathed in safe disinfectant on arrival and then individually housed in a high level hygiene HEPA filtered positive pressure facility. Socially, they could see and hear each other.
“They had contact with staff who were wearing hairnets, gloves and scrubs, which had been soaked in disinfectant and washed at a very high temperature. The isolator piglets were also on slats but were cleaned out every day and provided with disinfected ‘vetbed’ bedding twice a day. The isolator piglets were treated in a similar way to human infants.”
The researchers were able to demonstrate that, compared to their siblings in the isolator, the farm-reared piglets had reduced overall numbers of T-lymphocytes, the immune cells that drive immune responses in their intestinal tissues.
However, the piglets that had been exposed to natural surrounding dirt in the pen also had significantly increased numbers of a subset of these cells, the regulatory T-lymphocytes, which limit inflammation.
The shift in the ratio of stimulatory and regulatory cells seemed to have certain functional effects because the farm-reared piglets also showed decreased antibody responses to novel food proteins when they were weaned.
“By rearing piglets under different conditions, we have … demonstrated significant effects of environment on the intestinal microbiota, on host cells associated with the immune system and on gene expression,” wrote Lewis.
“Given the important role of regulatory T-cells in rodents, we hypothesized that their numbers would be altered by the conditions generated in our low-high hygiene model and that these differences would be reflected functionally in antibody responses to novel food protein. The results confirm this hypothesis and further demonstrate that neonatal piglets are a tractable model for human infants.”
Many mammal species besides humans have regulatory T-cells. They appear to be universal regulators of immune systems, and a reduction in their numbers is often associated with the development of allergies and autoimmune and inflammatory diseases.
“At this point, it is not exactly clear what caused the increased capacity for immune regulation in our farm-reared piglets,” said Lewis.
“Our previous work suggests that intestinal bacteria play a pivotal role in the development of a competent immune system and these bacteria are obtained from the environment during early life.”
The protective influences of the bacteria are sustained from that exposure in early life.
“We would very much like to rear piglets in the isolator and then put them back on the farm. However, this is not as easy as it sounds due to animal movement legislation,” she said.
“Our next step will be to look at the consequences of differences in the immune system caused by an early life rearing environment.”
Research is continuing. Additional work is required to find out the extent to which other farm-associated factors contributed to the impact of the environment on increased local and systemic immune regulation, such as social and maternal interactions, aerial contaminants, antigens from bedding and early nutrition.
