Children Raised on Farms Avert Allergies

Their Microbiomes Could Point to New Therapeutic Targets

Ingrid Hein

February 25, 2019

Infants raised on farms with environmental and animal diversity have enriched levels of bacteria in their gut microbiomes, which is associated with a lower risk for allergy and asthma, new research suggests.

"Just being raised on a farm is, in fact, correlated with changes in the gut," said investigator Julia Thorsen, MD, from the University of Wisconsin–Madison. But it turns out that "the type of farm an infant is exposed to is also an important factor in the development of the gut microbiome."

These study results offer clues for the development of new therapeutics, but it is early days for microbiome-modulating agents.

"We're getting ready for early-stage clinical trials, especially in areas where there would be the most impact, like asthma and allergies," Christina Ciaccio, MD, explained at the American Academy of Allergy, Asthma and Immunology 2019 Meeting in San Francisco.

But questions remain about safety and effectiveness that will challenge regulators, Ciaccio, who is from the University of Chicago, pointed out.

"I don't know if you can patent a probiotic cocktail or fiber supplements. It may be up to our partners in the pharmaceutical industry to see where we can have an impact," she explained.

In one study, researchers demonstrated that Akkermansia and Clostridia bacteria reduce gut inflammation and are associated with a lower risk for atopy and asthma in urban populations (Nat Med. 2016;22:1187-1191).

Comparing Stool Samples

"We wanted to see if the stools of infants raised on a farm were different than those of infants not raised on a farm," Thorsen told Medscape Medical News. "We didn't know the degree of farm exposure that would affect the stool."

Thorsen presented findings from a study of stool samples from infants born after 2013 and enrolled in the Wisconsin Infant Study Cohort (WISC) — 94 with farm exposure and 110 without.

Stool samples were collected when the infants were 2 months of age, and DNA was sequenced using the MiSeq System from Illumina. The investigators amplified the V4 region of the 16S ribosomal RNA. They extracted high-quality biomarker profiles from 89 farm infants and 102 nonfarm infants.

From the samples, Thorsen and her colleagues identified six differentially enriched taxa (P < .2 adjusted for false discovery rate). In stool samples from infants with farm exposure, members of the bacterial genera Akkermansia, Blautia, and Clostridiaceae were enriched. In contrast, in stool samples from infants without farm exposure, members of the genera Bifidobacterium, Veillonella, and Clostridium were enriched.

"Interestingly, the bacteria found to be more enriched in infants from diverse farms have also been found to be enriched in urban infants protected from atopic disease," Thorsen reported.

Simple farm exposure is associated with a lower prevalence of atopy and asthma (Nat Rev Immunol. 2010;10:861-868) but, to date, no data have shown that the type of farm makes a difference.

In their study, Thorsen and her colleagues found that stool microbiome communities were significantly different when they looked at three levels of exposure: highly diverse environment and animal exposure; highly diverse environment and moderately diverse animal (mostly cattle) exposure; and moderately to minimally diverse environmental and animal exposure.

Farm Diversity Affects Gut Microbiome

"Infants with exposure to a higher diversity of farm animals and environments, like hay and silage and raw farm milk, had a different proportion of microbial colonization patterns," said Thorsen. That proportion was in direct correlation to the diversity level of the farm.

"Not all farming environments are the same," she explained. "They are changing, especially when things that people used to do, like milking cows, are done by machines. These are other things we want to look into."

The team did not find any significant differences in the demographic characteristics previously hypothesized to affect the microbiome. Birth method (P = .41), the season a child was born (P = .40), and whether or not a child was breast-fed (P = .05) did not significantly affect the gut microbiome of the infants.

However, significantly more farm mothers than nonfarm mothers consumed unpasteurized milk during pregnancy (16% vs 2%; P = .0001).

"We don't know how this influences progress as the child grows up," Thorsen told Medscape Medical News. "We are still looking at trajectories we can identify or exposures we can pinpoint as being protective or nonprotective."

Thorsen and her colleagues plan to assess the infants again at 9 and 24 months to evaluate the association between gut microbiome and atopic disease and asthma. "I'm really excited about seeing how the microbiome progresses," she said.

Thorsen has disclosed no relevant financial relationships. Ciaccio is a medical advisor for Closcra Bio.

American Academy of Allergy, Asthma and Immunology (AAAAI) 2019 Meeting: Abstract 906. Presented February 25, 2019.

Follow Medscape on Twitter @Medscape and Ingrid Hein @ingridhein

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