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Gut Microbiome Maturation Plays Role in Reduced Asthma Risk in Infants Exposed to Farms

NEW YORK – Changes in the early gut microbiome may help protect young children growing up on farms against developing asthma through metabolites the microbes produce, a new analysis has found.

Researchers involved in a study called Protection against Allergy: Study in Rural Environments (PASTURE) examined the gut microbiomes of infants exposed to farm life and those not living on farms. The hygiene hypothesis has suggested that immune-mediated diseases like allergies and asthma have increased as people have left traditional lifstyles behind. Living on a farm is thought to protect against asthma through increased exposure to microbes, possibly through interactions with animals.

Markus Ege of the Ludwig Maximilian University of Munich in Germany and his colleagues generated and modeled 16S rRNA sequencing data from a cohort of more than 900 young children. As the researchers reported on Monday in Nature Medicine, exposure to farm settings before one year of age influenced the maturation of the infants' gut microbiomes and was linked to a reduced risk of developing asthma at school age. They additionally noted a link between bacteria that produce butyrate and protection against developing asthma.

"We found that a comparatively large part of the protective farm effect on childhood asthma was mediated by the maturation of the gut microbiome in the first year of life," first author Martin Depner from Helmholtz Zentrum München in Germany said in a statement. "This suggests that farm children are in contact with environmental factors, possibly environmental microbiota, that interact with the gut microbiome and lead to this protective effect."

Through PASTURE, researchers have been following a cohort of 930 European infants from birth, half of whom were born to mothers living on family-run farms. For this analysis, Depner and his colleagues collected fecal samples from infants at two months and 12 months of age for microbiome analysis.

At two months of age, the infants' gut microbiomes were predominantly composed of bacteria from the Bifidobacterium genus, which has been associated with breastfeeding. By 12 months of age, though, the portion of Bifidobacterium was halved and Blautia, Coprococcus, Faecalibacterium, and Roseburia bacteria increased in abundance.

The researchers generated a model, which they dubbed EMA (estimated microbiome age), to assess the age of a healthy microbiome. This model, they noted, reflects microbiome maturation between the ages of two and 12 months. Prior to two months' of age, the gut microbiome is largely influenced by mode of birth and breastfeeding, they noted, but after that, it is increasingly influenced by environmental exposures.

On average, children with asthma had lower EMA scores at 12 months' of age, a finding the researchers validated in an additional set of 102 children. They further calculated that the EMA model mediates about 19 percent of the protective farm effect.

The researchers additionally found an inverse association between asthma and fecal butyrate levels. In mice, butyrate, a short chain fatty acid, helps protect against asthma. They homed in on two taxa — Roseburia and Coprococcus — that can both produce butyrate and contribute to asthma protection. The researchers noted that these bacteria do not appear to be protective against asthma on their own, but may represent a network of bacteria that produce protective short chain fatty acids.

"A mature gut microbiome with a high level of short chain fatty acids had a protective effect on the respiratory health of the children in this study. This suggests the idea of a relevant gut-lung axis in humans," Ege said in a statement. "This also means, however, that an immature gut microbiome may contribute to the development of diseases. This emphasizes the need for prevention strategies in the first year of life, when the gut microbiome is highly plastic and amenable to modification."