Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma.

Abstract

Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. 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 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), we found inverse associations of asthma 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) and 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.

• Authors: Martin Depner, Diana Hazard Taft, Pirkka V Kirjavainen, Karen M Kalanetra, Anne M Karvonen, Stefanie Peschel, Elisabeth Schmausser-Hechfellner, Caroline Roduit, Remo Frei, Roger Lauener, Amandine Divaret-Chauveau, Jean-Charles Dalphin, Josef Riedler, Marjut Roponen, Michael Kabesch, Harald Renz, Juha Pekkanen, Freda M Farquharson, Petra Louis, David A Mills, Erika von Mutius, PASTURE study group, Markus J Ege
• Journal: Nature medicine (Nat Med) Vol. 26 Issue 11 Pg. 1766-1775 (11 2020) ISSN: 1546-170X [Electronic] United States
• PMID: 33139948 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Butyrates
• RNA, Ribosomal, 16S
• Coenzyme A-Transferases
• butyryl-CoA acetoacetate CoA transferase

Topics

• Adolescent
• Asthma (epidemiology, genetics, microbiology, pathology)
• Bacteria (classification, genetics, metabolism)
• Butyrates (isolation & purification, metabolism)
• Child
• Coenzyme A-Transferases (genetics)
• Feces (chemistry)
• Female
• Gastrointestinal Microbiome (genetics)
• Humans
• Infant
• Lung (metabolism, pathology)
• Male
• RNA, Ribosomal, 16S (genetics)