Decoding the diagnostic and therapeutic potential of microbiota using pan-body pan-disease microbiomics

Georges P. Schmartz, Jacqueline Rehner, Madline P. Gund, Verena Keller, Leidy-Alejandra G. Molano, Stefan Rupf, Matthias Hannig, Tim Berger, Elias Flockerzi, Berthold Seitz, Sara Fleser, Sabina Schmitt-Grohé, Sandra Kalefack, Michael Zemlin, Michael Kunz, Felix Götzinger, Caroline Gevaerd, Thomas Vogt, Jörg Reichrath, Lisa Diehl, Anne Hecksteden, Tim Meyer, Christian Herr, Alexey Gurevich, Daniel Krug, Julian Hegemann, Kenan Bozhueyuek, Tobias A. M. Gulder, Chengzhang Fu, Christine Beemelmanns, Jörn M. Schattenberg, Olga V. Kalinina, Anouck Becker, Marcus Unger, Nicole Ludwig, Martina Seibert, Marie-Louise Stein, Nikolas Loka Hanna, Marie-Christin Martin, Felix Mahfoud, Marcin Krawczyk, Sören L. Becker, Rolf Müller, Robert Bals and Andreas Keller ()
Additional contact information
Georges P. Schmartz: Saarland University
Jacqueline Rehner: Saarland University
Madline P. Gund: Saarland University
Verena Keller: Saarland University Medical Center
Leidy-Alejandra G. Molano: Saarland University
Stefan Rupf: Saarland University
Matthias Hannig: Saarland University
Tim Berger: Saarland University Medical Center
Elias Flockerzi: Saarland University Medical Center
Berthold Seitz: Saarland University Medical Center
Sara Fleser: Saarland University
Sabina Schmitt-Grohé: Saarland University
Sandra Kalefack: Saarland University
Michael Zemlin: Saarland University
Michael Kunz: Saarland University Hospital
Felix Götzinger: Saarland University Hospital
Caroline Gevaerd: and Allergology
Thomas Vogt: and Allergology
Jörg Reichrath: and Allergology
Lisa Diehl: Saarland University
Anne Hecksteden: Saarland University
Tim Meyer: Saarland University
Christian Herr: Saarland University
Alexey Gurevich: Helmholtz Institute for Pharmaceutical Research Saarland
Daniel Krug: Helmholtz Institute for Pharmaceutical Research Saarland
Julian Hegemann: Helmholtz Institute for Pharmaceutical Research Saarland
Kenan Bozhueyuek: Helmholtz Institute for Pharmaceutical Research Saarland
Tobias A. M. Gulder: Helmholtz Institute for Pharmaceutical Research Saarland
Chengzhang Fu: Helmholtz Institute for Pharmaceutical Research Saarland
Christine Beemelmanns: Helmholtz Institute for Pharmaceutical Research Saarland
Jörn M. Schattenberg: Saarland University Medical Center
Olga V. Kalinina: Helmholtz Institute for Pharmaceutical Research Saarland
Anouck Becker: Saarland University Medical Center
Marcus Unger: Saarland University Medical Center
Nicole Ludwig: Saarland University
Martina Seibert: Saarland University Medical Center
Marie-Louise Stein: Saarland University Medical Center
Nikolas Loka Hanna: Saarland University
Marie-Christin Martin: Saarland University Medical Center
Felix Mahfoud: Saarland University Hospital
Marcin Krawczyk: Saarland University Medical Center
Sören L. Becker: Saarland University
Rolf Müller: Helmholtz Institute for Pharmaceutical Research Saarland
Robert Bals: Saarland University
Andreas Keller: Saarland University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.3 gigabases. Collected from 515 patients, these samples yield an average of 3.7 metagenomes per patient. Our results suggest significant microbial variations across diseases and specimen types, including unexpected anatomical sites. We identify 583 unexplored species-level genome bins (SGBs) of which 189 are significantly disease-associated. Of note, the existence of microbial resistance genes in one specimen was indicative of the same resistance genes in other specimens of the same patient. Annotated and previously undescribed SGBs collectively harbor 28,315 potential biosynthetic gene clusters (BGCs), with 1050 significant correlations to diseases. Our combinatorial approach identifies distinct SGBs and BGCs, emphasizing the value of pan-body pan-disease microbiomics as a source for diagnostic and therapeutic strategies.

Date: 2024
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DOI: 10.1038/s41467-024-52598-7

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