Farm Effect

Un bambino con cappellino si occupa delle vacche giocando con loro e portandogli il fieno nelle mangiatoie

Numerous epidemiological studies have shown that children who grow up on traditional farms are protected from asthma, hay fever and allergic sensitization (Pechlivanis & von Mutius, Acta Med Acad 2020). Early-life contact with livestock, particularly exposure to cow sheds, as well as the consumption of unprocessed cow’s milk have been identified as the most effective protective exposures.

The leitmotiv of all these studies is an interaction of the human immune system with microbial exposure. Recently we have seen that the farm environment fosters the maturation of the intestinal microbiome, which again protects from the development of asthma (Depner et al, Nature Medicine 2020). We estimated a microbiome age (EMA) based on compositional changes in the gut microbiome. EMA mediated the asthma-protective effect of farm exposure by about 20%. By the end of the first year of life, the maturational process resulted in an abundance of fermenting bacteria, which produce beneficial short chain fatty acids such as butyrate and propionate.

young boy using an asthma inhaler outdoors

Already at 2 months of life, however, a healthy gut microbiome exerts protective effects on asthma. Likewise, a distinct composition of different species and strains within the genus Bifidobacterium protects from persistent rash and atopic eczema, a known asthma comorbidity. While the typical Bifidobacterium composition at 2 months is inversely related to atopic eczema and persistent rash, the typical composition at 12 months is not and may even create a risk for late-onset rash (Depner et al, PAI 2025). This demonstrates that successful prevention strategies with Bifidobacterium as a probiotic must consider the relevant window of opportunity and the adequate subgenus composition.

Currently we are investigating deeper into the mechanisms behind the protective farm effect. We aim to answer the following research questions:

What is the role of environmental bacteria in asthma protection?
Are there any other microorganisms involved in the protective effect?
Which bacterial metabolites are involved in the protective effect of the gut microbiome?
How does microbial exposure on a farm affect the human immune system?
Does the farm exposure operate through epigenetic modifications?

VIRO, Virology, Research Unit Microbial Diseases Prevention (Li Deng)

COMI, Research Unit Comparative Microbiome Analysis (Michael Schloter)

BGC, Analytical Biogeochemistry (Philippe Schmitt-Kopplin)

University of California, Davis (Diana Hazard Taft)

University of California at San Diego (Rob Knight, Pieter C. Dorrestein)

Leipzig University (Jon Genuneit)

University of Bourgogne Franche-Comté (Amandine Divaret-Chauveau)

University of Bern (Caroline Roduit)

Finnish Institute for Health and Welfare (Anne M. Karvonen)

Prof. Dr. Markus Ege

MA MPH, Group Leader

Dr. rer. biol. hum. Martin Depner

Biostatistician

Dr. Giulia Pagani

Bioinformatician

PD Dr. sc. hum. Sonali Pechlivanis

Epidemiologist

Birgit Langer

Data Manager

Elisabeth Schmaußer-Hechfellner

Data Manager

Christine Strunz-Lehner

Technical Support

Depner, M. ; Taft, D.H. ; Peschel, S. ; Roduit, C. ; Karvonen, A.M. ; Barnig, C. ; Divaret-Chauveau, A. ; Riedler, J. ; Pekkanen, J. ; Schmaußer-Hechfellner, E. ; Pagani, G. ; Lauener, R. ; Roponen, M. ; Renz, H. ; Pfefferle, P.I. ; Schaub, B. ; von Mutius, E. ; Kirjavainen, P.V. ; Ege, M.J.

The Janus face of Bifidobacterium in the development of atopic eczema: A role for compositional maturation.

Blandino, A. ; Scherer, D. ; Boekstegers, F. ; Rounge, T.B. ; Langseth, H. ; Roessler, S. ; Hveem, K. ; Brenner, H. ; Pechlivanis, S. ; Waldenberger, M. ; Lorenzo Bermejo, J.

Small-RNA sequencing reveals potential serum biomarkers for gallbladder cancer: Results from a three-stage collaborative study of large European prospective cohorts.

Mohren, L. ; Erdlenbruch, F. ; Leitão, E. ; Kilpert, F. ; Hönes, G.S. ; Kaya, S. ; Schröder, C. ; Thieme, A. ; Sturm, M. ; Park, J. ; Schlüter, A. ; Ruiz, M. ; Morales de la Prida, M. ; Casasnovas, C. ; Becker, K. ; Roggenbuck, U. ; Pechlivanis, S. ; Kaiser, F.J. ; Synofzik, M. ; Wirth, T. ; Anheim, M. ; Haack, T.B. ; Lockhart, P.J. ; Jöckel, K.H. ; Pujol, A. ; Klebe, S. ; Timmann, D. ; Depienne, C.

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.

Pechlivanis, S. ; Schmaußer-Hechfellner, E. ; Schaub, B. ; Skevaki, C. ; Barnig, C. ; Roduit, C. ; Divaret-Chauveau, A. ; Karvonen, A.M. ; Riedler, J. ; Illi, S. ; von Mutius, E.

Impaired skin barrier and allergic sensitization in 16-year-old adolescents.

Tannemann, N. ; Erbel, R. ; Nöthen, M.M. ; Jöckel, K.H. ; Pechlivanis, S.

Genetic polymorphisms affecting telomere length and their association with cardiovascular disease in the Heinz-Nixdorf-Recall study.

Böck, A. ; Urner, K. ; Eckert, J.K. ; Salvermoser, M. ; Laubhahn, K. ; Kunze, S. ; Kumbrink, J. ; Hoeppner, M.P. ; Kalkbrenner, K. ; Kreimeier, S. ; Beyer, K. ; Hamelmann, E. ; Kabesch, M. ; Depner, M. ; Hansen, G. ; Riedler, J. ; Roponen, M. ; Schmaußer-Hechfellner, E. ; Barnig, C. ; Divaret-Chauveau, A. ; Karvonen, A.M. ; Pekkanen, J. ; Frei, R. ; Roduit, C. ; Lauener, R. ; Schaub, B. ; PASTURE Study Group (Illi, S. ; Pechlivanis, S. ; Pagani, G. ; Ege, M.J.)

An integrated molecular risk score early in life for subsequent childhood asthma risk.

Marques Dos Santos, M. ; Pivniouk, V. ; Rankl, B. ; Walker, A. ; Pagani, G. ; Hertkorn, N. ; Schmitt-Kopplin, P. ; Müller, C. ; Bracher, F. ; Merl-Pham, J. ; Hauck, S.M. ; Schloter, M. ; Michael, A.N. ; Anderson, D. ; Honeker, L. ; Gozdz, J. ; Pivniouk, O. ; Ober, C. ; Holbreich, M. ; Martinez, F.D. ; Snyder, S.A. ; von Mutius, E. ; Vercelli, D.

Asthma-protective agents in dust from traditional farm environments.

Ullmann, T. ; Peschel, S. ; Finger, P. ; Müller, C.L. ; Boulesteix, A.L.

Over-optimism in unsupervised microbiome analysis: Insights from network learning and clustering.

The Farm Effect – Protection by microbial exposure

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