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In the 1990s, a Swiss physician noticed something intriguing: Children in his practice who lived on farms seemed to have far fewer respiratory allergies than non-farm kids. He teamed with local researchers to probe this observation more rigorously, and sure enough, they found that it held weight — and has for decades.

Today, more than one tenth of children in modern industrialized countries suffer from asthma, and about a third have allergic rhinitis. Large studies conducted in Canada and Europe (Midodzi et al and Illi et al) suggest that asthma rates are 32% to 78% lower among children who live in rural farming environments.

Some of the most dramatic findings was reported in 2016 in The New England Journal of Medicine. In a study that compared 60 US Amish and Hutterite farm children — two groups with similar genetic ancestries and lifestyles — asthma rates were four times lower and allergic sensitization (ie, serum IgE against common allergens) was six times lower among the Amish children.

The two farming communities share broad similarities, but there is a key difference: Amish live on single-family dairy farms and use horses for fieldwork and transportation, whereas Hutterites live and work on large, industrialized farms. As a result, furosemide conducto arterioso as Amish children grow up, they have more contact with animals. They also start eating solid foods earlier and eat a more varied diet that includes raw, unprocessed milk.

It’s hard to pinpoint exactly what confers protection from asthma and allergies. Something in the environment? Something in the diet? Does it have something to do with farm animals? It is likely that “it’s a mixture of all of them,” said Remo Frei, PhD, an immunologist with the Christine Kuhne–Center for Allergy Research and Education (CK-CARE) — a research network in Switzerland with locations in Davos, Munich, and Zurich.

Summarized in a single word, “it’s ‘diversity’ — diversity of their exposures from animals and microbes,” said Caroline Roduit, MD, MPH, PhD, a pediatric allergist and epidemiologist at CK-CARE. Roduit and Frei summarized the latest research on the “farm effect” in a review published in June 2022 in Pediatric Allergy and Immunology. They spoke about it in interviews with Medscape Medical News.

Origins

The “farm effect” dovetails with the commonly known hygiene hypothesis, a concept introduced in 1989 to explain the rapid rise of atopic diseases in westernized countries. Researchers at the time found that children from large families had fewer allergic diseases. They surmised that having more siblings increased their exposure to infections, which in turn protected them from asthma and allergies.

Today, this hypothesis centers on the microbiome. A growing body of research suggests that a variety of environmental and lifestyle factors converge to disrupt the body’s natural community of microbes. These disruptions prevent valuable crosstalk between microbiota and innate immune cells that helps establish immune tolerance. In essence, microbial exposures during the first year of life, especially in the first few months and even in utero, train the body not to react against allergens and other harmless substances.

“Early exposure to good microbes — microbes that our immune system most likely evolved to deal with — is what protects [farm children] from asthma and allergies,” said Donata Vercelli, MD, professor of cellular and molecular medicine at the University of Arizona, in an interview with Medscape. This evolution took place over hundreds of thousands of years, and our immune system has not yet adapted to modern urban conditions, which are “very recent in evolutionary times,” she notes. Farming environments are “much closer to that initial setup that our immune system evolved to deal with.”

Something in the Air

From an early age, farm children inhale a range of substances that city kids rarely encounter — microbial products from livestock and other animals.

In the 2016 analysis of farm children, median levels of endotoxins (bacterial toxins) were 6.8 times higher in dust samples from Amish homes, where children suffered asthma and allergic sensitization at rates 4 and 6 times lower than their Hutterite counterparts. Perhaps even more remarkable, the researchers showed they could prevent airway hyperreactivity in mice by treating them intranasally with dust from Amish homes — but not from Hutterite homes. But the Amish dust offered no such benefit to mice that were genetically deficient in two innate immune molecules (MyD88 and Trif), suggesting that farm-related protection from atopic disease requires an effective innate immune system.

“We don’t yet know about all the pathways involved, but we know that ultimately, they converge on the basic signaling of innate immunity,” said Vercelli, who helped lead the 2016 study.

A 2014 study of urban US children found that homes of children with atopy or atopic wheeze had less bacterial richness — reflecting reduced numbers of bacterial taxa per dust sample. Interestingly, these health conditions were associated with reduced exposure to specific Firmicutes and Bacteriodetes bacteria present in house dust during the first year of life. The findings suggest that “the type of environmental factors are also important,” said Roduit. “It’s not just diversity but what kind of diversity.”

Diet Research

Diet seems to be another key factor. Children raised on farms often drink raw cow’s milk, whereas urban children typically drink pasteurized milk. “If it’s more processed, maybe you reduce certain good bacteria,” Roduit said. “Fiber is also removed during processing.”

A wave of research shows that what children consume during their early months and years can influence their risk of developing conditions known as the “atopic march” — eczema, allergic rhinitis, asthma, and food allergy.

Carina Venter, PhD, RD, associate professor in allergy and immunology at the University of Colorado in Denver, and her colleagues investigated whether having a diverse diet during infancy had an impact on the development of food allergies. They analyzed a cohort of 969 children who were born in the Isle of Wight, in the United Kingdom, from 2001 to 2002. The children were followed prospectively for a decade. Families completed questionnaires about infant feeding at 3, 6, 9, and 12 months, and children underwent clinical examinations and skin prick tests for allergies to milk, wheat, egg, cod, peanut, and sesame at 1, 2, 3, and 10 years.

The decade-long study, published in 2020, found that for each additional food introduced by 6 months of age, the child’s risk of developing food allergies by age 10 dropped about 10%. Additional allergenic food consumed by 1 year reduced the risk of food allergies by 30%. Studies from China and Europe support that trend: food diversity in the first few years of life protects against development of allergic diseases.

“Feed a New Food Every Time the Baby Is Happy”

To delay or possibly prevent allergies and asthma in children, the American Academy of Allergy, Asthma and Immunology recommends introducing a range of healthy solid foods starting at age 4 to 6 months — including common allergens (egg, dairy, peanut, tree nuts, fish, and shellfish). “Every new food helps,” said Venter. “Feed a new food every time the baby is happy.”

As much as possible, the consumption of processed foods should be minimized. Processing removes healthy fiber and reduces microbial content, which can help preserve food but can also deplete beneficial bacteria.

There is no evidence that restricting a mother’s diet during pregnancy or while breastfeeding helps protect the child from developing allergies. More details and links to published studies can be found in a consensus document published in 2020 by North American allergy societies.

Another suggestion is to spend time outdoors. Growing evidence suggests that in addition to diet diversity, much of the farm-related protection against asthma and allergies comes from early exposure to nature and animals. Getting a pet may also help, though that evidence is less clear.

Ongoing Research

Vercelli’s team initiated efforts to translate the findings from the 2016 study of Amish and Hutterite children for children who do not have the benefit of growing up on a farm. They launched the ORBEX study to test whether giving a daily capsule of Broncho-Vaxom — an oral extract containing eight kinds of bacteria involved in respiratory infections — can prevent or delay the development of asthma in young children. The study is underway, although it was set back somewhat by the COVID pandemic, Vercelli said.

A study by Vercelli and colleagues that was conducted in mice showed that administering these microbial products into the airway protected the animals from experimental allergic asthma. Eventually the team would like to test intranasal application of the microbial extracts in people.

Leveraging the effects of microbes is a promising area of ongoing investigation. However, “the microbiome is a very dynamic entity,” Vercelli said. “If you give something, you have to ask what it does to the other microbes that are present. It’s not simple.”

Carina Venter has received grants from Reckitt Benckiser, Food Allergy Research and Education, and the National Peanut Board; and personal fees from Reckitt Benckiser, the Nestle Nutrition Institute, Danone, Abbott Nutrition, Else Nutrition, and Before Brands. Donata Vercelli is an inventor in PCT/US2021/016918, entitled “Therapeutic Fractions and Proteins from Asthma-Protective Farm Dust”; PCT/EP2019/085016, entitled “Barn Dust Extract for the Prevention and Treatment of Diseases”; and PCT/EP2019/074562, entitled, “Method of Treating and/or Preventing Asthma, Asthma Exacerbations, Allergic Asthma and/or Associated Conditions with Microbiota Related to Respiratory Disorders”. Vercelli was supported by grants from the National Institutes of Health. Her lab was funded in part by a research grant from OM Pharma SA to the University of Arizona. Frei and Roduit have disclosed no relevant financial relaitonships.

Esther Landhuis is a freelance science journalist in the San Francisco Bay Area. She can be found on Twitter @elandhuis.

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