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The Farm Effect – Protective microbiome for children living on farms

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Numerous epidemiological studies have shown that children who grow up on traditional farms are protected from asthma, hay fever and allergic sensitization. Early-life contact with livestock, especially contact to cow sheds as well as the consumption of unprocessed cow’s milk have been identified as the most effective protective exposures. Studies of the immunobiology of farm living point to activation and modulation of innate and adaptive immune responses especially by intense microbial exposures. Farms are environments that afford a wide range of microbial exposures. This raises the question if we can find protective microorganisms in a farming environment and, if (how) we can explain the farm effect with the influence of bacteria or other microorganisms living on the farm.

The overarching aim of our microbiome analysis is to find relevant associations between microbiota and allergic diseases (hay fever/asthma/atopic dermatitis/food allergy). This is mostly done by using samples from different sites in different studies (farm or clinical). Environmental samples are mainly coming from the children’s mattress dust or were explicitly taken in typical farm environments like animal sheds. Levels of endotoxin (a lipopolysaccharide, LPS) found in the cell wall of bacteria from the child's mattress were inversely related to asthma. Microbial richness, i.e. the number of fungi or bacteria found in the environment of children, was positively associated with a farm environment and inversely associated with asthma. By modeling differences in house dust microbiota composition between farm and non-farm homes it could be shown that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases.

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Although the environmental exposures are highly relevant and might at least partly transit to the body, microbes direct living on/in our body intuitively seem stronger involved in disease processes. This concerns different body sites. While the respiratory tract is the obvious target for respiratory diseases, the skin might be more relevant for atopic dermatitis, the gut for food allergy. Moreover the concept of a gut-lung or a gut-skin axis highlights the importance of the gut microbiome. We could show that the early maturation of the gut microbiome during the first year of life contributes to the protective effect of farming on childhood asthma. Also a higher cytokine activation by consumption of unprocessed cow’s milk was in part mediated by the gut microbiome. Looking at the upper respiratory tract, differences between asthmatics and healthy controls are more seen in the nose than in the throat. Now, there is ongoing work to further disentangle microorganisms or their interactions which are associated with allergic diseases.

Networks and Cooperations

NeTCoMi - network construction and comparison for microbiome data in R:

Publication - https://pubmed.ncbi.nlm.nih.gov/33264391/
Stefanie Peschel: https://github.com/stefpeschel/NetCoMi
Christian Müller Group - https://www.statistik.uni-muenchen.de/personen/professoren/mueller/index.html
Anne-Laure Boulesteix, IBE, LMU - https://www.ibe.med.uni-muenchen.de/mitarbeiter/professoren/boulesteix/index.html 

COMI, Research Unit Comparative Microbiome Analysis, Michael Schloter

Scientists

Dr. rer. biol. hum. Martin Depner

Biostatistiker

Dr. Giulia Pagani

Bioinformatikerin

PD Dr. sc. hum. Sonali Pechlivanis

Epidemiologin

Prof. Dr. Markus Ege

Wissenschaftlicher Mitarbeiter

Birgit Langer

Datenmanagerin

Elisabeth Schmaußer-Hechfellner

Datenmanagerin

Publications

Read more

2022 Scientific Article in Blood

Schuetz, C. ; Gerke, J.S. ; Ege, M.J. ; Walter, J. ; Kusters, M. ; Worth, A. ; Kanakry, J.A. ; Dimitrova, D. ; Wolska-Kuśnierz, B. ; Chen, K. ; Unal, E. ; Karakukcu, M. ; Pashchenko, O. ; Leiding, J. ; Kawai, T. ; Amrolia, P.J. ; Berghuis, D. ; Buechner, J. ; Buchbinder, D. ; Cowan, M.J. ; Gennery, A.R. ; Güngör, T. ; Heimall, J. ; Miano, M. ; Meyts, I. ; Morris, E.C. ; Riviere, J. ; Sharapova, S.O. ; Shaw, P.J. ; Slatter, M. ; Hönig, M. ; Veys, P. ; Fischer, A. ; Cavazzana, M. ; Moshous, D. ; Schulz, A. ; Albert, M.H. ; Puck, J.M. ; Lankester, A.C. ; Notarangelo, L.D. ; Neven, B.

Hypomorphic RAG deficiency: Impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT.

2022 Scientific Article in American Journal of Respiratory and Critical Care Medicine

Illi, S. ; Depner, M. ; Pfefferle, P.I. ; Renz, H. ; Roduit, C. ; Taft, D.H. ; Kalanetra, K.M. ; Mills, D.A. ; Farquharson, F.M. ; Louis, P. ; Schmaußer-Hechfellner, E. ; Divaret-Chauveau, A. ; Lauener, R. ; Karvonen, A.M. ; Pekkanen, J. ; Kirjavainen, P.V. ; Roponen, M. ; Riedler, J. ; Kabesch, M. ; Schaub, B. ; von Mutius, E.

Immune responsiveness to LPS determines risk of childhood wheeze and asthma in 17q21 risk allele carriers.

Contact

Dr. rer. biol. hum. Martin Depner

Biostatistiker