Asthma Protection and Gut Microbiome

Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown.

Gut microbiome changes during the first year of life reveal that microbiome maturation may contribute to asthma protection during childhood, according to a study published in Nature Medicine. The results further indicate that the estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure and reduced risk of asthma at school age.

Asthma was defined as a physician's diagnosis of asthma or recurrent obstructive bronchitis established until six years of age and was present in 8.1 percent of the 930 children. A highly diverse microbial environment may influence the human microbiome and thus mitigate asthma risk, as shown in the microbiome of the upper airways. For the gut microbiome, the effect on airway disease is less obvious.

The human gut microbiome undergoes profound changes during the first year of life and starts stabilizing soon thereafter. Hence, the researchers hypothesized that the first year of life, in particular, represents a time window during which exposures to the outer environment shape the development of the human microbiome with possible lasting consequences.

In the Protection against Allergy: Study in Rural Environments (PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age.

The analysis included 930 children from a European cohort population, of whom half lived in rural areas. The researchers collected fecal samples at months two and 12, and obtained sequence reads for bacterial 16S rRNA and the fungal internal transcribed spacer (ITS) region from samples from 618 and 189 children, respectively, to comprehensively assess farm-related environmental effects on the early gut microbiome.

Data Analysis Findings

• The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (β = 0.27 (0.12–0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56–0.93), P = 0.011).
• EMA mediated the protective farm effect by 19%.
• In a nested case–control sample (n = 138), inverse associations of asthma were found with:
  • The measured level of fecal butyrate (OR = 0.28 (0.09–0.91), P = 0.034).
  • Bacterial taxa that predict butyrate production (OR = 0.38 (0.17–0.84), P = 0.017).
  • The relative abundance of the gene encoding butyryl–coenzyme A (CoA):acetate–CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19–0.97), P = 0.042).

The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut–lung axis in humans.

These findings suggest that farm-related exposures influenced the maturation of the gut microbiome during the time window from two to 12 months. As a measure of maturation, EMA mediated a substantial proportion of the well-known farm effect on asthma, thereby suggesting a gut-lung axis in humans.

For the full article, follow the link: https://doi.org/10.1038/s41591-020-1095-x.

Primary source: Nature Medicine