Impact of diet and host genetics on the murine intestinal mycobiome

Yask Gupta, Anna Lara Ernst, Artem Vorobyev, Foteini Beltsiou, Detlef Zillikens, Katja Bieber, Simone Sanna-Cherchi, Angela M. Christiano, Christian D. Sadik, Ralf J. Ludwig*, Tanya Sezin*

*Corresponding author for this work
16 Citations (Scopus)

Abstract

The mammalian gut is home to a diverse microbial ecosystem, whose composition affects various physiological traits of the host. Next-generation sequencing-based metagenomic approaches demonstrated how the interplay of host genetics, bacteria, and environmental factors shape complex traits and clinical outcomes. However, the role of fungi in these complex interactions remains understudied. Here, using 228 males and 363 females from an advanced-intercross mouse line, we provide evidence that fungi are regulated by host genetics. In addition, we map quantitative trait loci associated with various fungal species to single genes in mice using whole genome sequencing and genotyping. Moreover, we show that diet and its’ interaction with host genetics alter the composition of fungi in outbred mice, and identify fungal indicator species associated with different dietary regimes. Collectively, in this work, we uncover an association of the intestinal fungal community with host genetics and a regulatory role of diet in this ecological niche.

Original languageEnglish
Article number834
JournalNature Communications
Volume14
Issue number1
ISSN1751-8628
DOIs
Publication statusPublished - 14.02.2023

Funding

Foremost we are grateful for the mentorship and continued support we had received from the late Detlef Zillikens. His inspiring enthusiasm and dedication to research will be deeply missed. This work has been financially supported by the Juniorförderung grant “Characterization of host genetics, diet and microbiome interplay in systemic lupus erythematosus” awarded by the University of Lübeck (YG), as well as Cluster of Excellence Precision Medicine in Chronic Inflammation (EXC 2167), the Collaborative Research Center Pathomechanisms of Antibody-mediated Autoimmunity (SFB 1526), Research Training Groups Modulation of Autoimmunity (GRK1727) (AV), Genes Environment and Inflammation (GRK1743) (AV), and the clinician scientist program (Deutsche Dermatologische Gesellschaft/ Arbeitsgemeinschaft Dermatologische Forschung) (AV), all from the Deutsche Forschungsgemeinschaft and from the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig Holstein.

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

  • 2.21-05 Immunology

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  • CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

    Sadik, C. (Speaker, Coordinator), Zillikens, D. (Speaker, Coordinator), Scheffold, A. (Principal Investigator (PI)), Schmidt, E. (Principal Investigator (PI)), Heine, G. (Principal Investigator (PI)), Manz, R. (Principal Investigator (PI)), Köhl, J. (Principal Investigator (PI)), Ludwig, R. (Principal Investigator (PI)), Peipp, M. (Principal Investigator (PI)), Hammers, M. C. (Principal Investigator (PI)), Verschoor, A. (Principal Investigator (PI)), Karsten, C. (Principal Investigator (PI)), Nimmerjahn, F. (Principal Investigator (PI)), Hutloff, A. (Principal Investigator (PI)), Ibrahim, S. (Principal Investigator (PI)), Wettschureck, N. (Principal Investigator (PI)), Bieber, K. (Principal Investigator (PI)), Schilf, P. (Principal Investigator (PI)), Vaeth, M. (Principal Investigator (PI)), Hirose, M. (Principal Investigator (PI)), Vaeth, M. (Principal Investigator (PI)), Baines, J. F. (Principal Investigator (PI)), Bacher, P. (Principal Investigator (PI)), Hoffmann, M. (Principal Investigator (PI)), Busch, H. S. (Principal Investigator (PI)), Höppner, M. (Principal Investigator (PI)), Becker, M. (Principal Investigator (PI)), Holtsche, M. M. (Principal Investigator (PI)), Fähnrich, A. (Principal Investigator (PI)), Szymczak, S. (Principal Investigator (PI)), Murthy, S. (Principal Investigator (PI)) & Lux, A. (Principal Investigator (PI))

    01.01.22 → …

    Project: DFG Joint ResearchDFG Collaborative Research Centers (CRC)

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