Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma
Authors: Petra I Pfefferle
Diana Hazard Taft
Marjut Roponen
Lucie Laurent
Jean-Charles Dalphin
PASTURE study group
Josef Riedler
Remo Frei
Martin Depner
Anne M Karvonen
David A Mills
Michael Kabesch
Bianca Schaub
Juha Pekkanen
Amandine Divaret-Chauveau
Jon Genuneit
Markus J Ege
Stefanie Peschel
Erika von Mutius
Pirkka V Kirjavainen
Harald Renz
Karen M Kalanetra
Sabina Illi
Anne Hyvärinen
Freda M Farquharson
Elisabeth Schmausser-Hechfellner
Caroline Roduit
Petra Louis
Roger Lauener
Journal: Nature Medicine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: farm exposure; asthma; gut microbiome; infants; butyrate
Affiliations: Institute for Asthma and Allergy Prevention, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Department of Food Science & Technology, University of California Davis, Davis, CA, USA., Department of Health Security, Finnish Institute for Health and Welfare, Kuopio, Finland., Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland., Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland., Children's Hospital, University of Zürich, Zurich, Switzerland., Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland., Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland., University of Zürich, Zurich, Switzerland., School of Medicine, University of St. Gallen, St. Gallen, Switzerland., Pediatric Allergy Department, Children's Hospital, University Hospital of Nancy, Vandoeuvre les Nancy, France., EA 3450 DevAH, Faculty of Medicine, University of Lorraine, Vandoeuvre les Nancy, France., Department of Respiratory Disease, UMR CNRS 6249 Chrono-environnement, University Hospital of Besançon, Besançon, France., Children's Hospital, Schwarzach, Austria., Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland., KUNO Children's University Hospital Regensburg, Department of Pediatric Pneumology and Allergy, Regensburg, Germany., Department of Clinical Chemistry and Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany., German Center for Lung Research., Department of Public Health, University of Helsinki, Helsinki, Finland., The Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK., Dr. von Hauner Children's Hospital, Ludwig Maximilian University of Munich, Munich, Germany., German Center for Lung Research, . ., Dr. von Hauner Children's Hospital, Ludwig Maximilian University of Munich, Munich, Germany. .

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. 

Retracted: No

PubPeer comments:
 In the present PASTURE subpopulation farm children did not have a significant lower risk of asthma as compared to non- farm children. This may have been expected by the [largest study] so far) that even showed an increased risk. The authors nevertheless construct here some microbiome score. As that also largely failed [by current recommendations] the speculation about any new gut-lung axis is certainly not warranted. ![file] ,