Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity.
Gut microbial dysbioses are linked to aberrant immune responses, which are often accompanied by abnormal production of inflammatory cytokines. As part of the Human Functional Genomics Project (HFGP), we investigate how differences in composition and function of gut microbial communities may contribute to inter-individual variation in cytokine responses to microbial stimulations in healthy humans. We observe microbiome-cytokine interaction patterns that are stimulus specific, cytokine specific, and cytokine and stimulus specific. Validation of two predicted host-microbial interactions reveal that TNFα and IFNγ production are associated with specific microbial metabolic pathways: palmitoleic acid metabolism and tryptophan degradation to tryptophol. Besides providing a resource of predicted microbially derived mediators that influence immune phenotypes in response to common microorganisms, these data can help to define principles for understanding disease susceptibility. The three HFGP studies presented in this issue lay the groundwork for further studies aimed at understanding the interplay between microbial, genetic, and environmental factors in the regulation of the immune response in humans. PAPERCLIP.
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Melanie
M
Schirmer
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, 6525 GA Nijmegen, the Netherlands.
Sanne P
SP
Smeekens
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Hera
H
Vlamakis
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, 6525 GA Nijmegen, the Netherlands.
Martin
M
Jaeger
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, 6525 GA Nijmegen, the Netherlands.
Marije
M
Oosting
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Eric A
EA
Franzosa
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, 6525 GA Nijmegen, the Netherlands.
Rob
R
Ter Horst
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, 6525 GA Nijmegen, the Netherlands.
Trees
T
Jansen
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, 6525 GA Nijmegen, the Netherlands.
Liesbeth
L
Jacobs
Department of Genetics, University of Groningen, University Medical Center Groningen, 9713 EX Groningen, the Netherlands.
Marc Jan
MJ
Bonder
Department of Genetics, University of Groningen, University Medical Center Groningen, 9713 EX Groningen, the Netherlands; Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk 630090, Russia; Novosibirsk State University, Novosibirsk 630090, Russia.
Alexander
A
Kurilshikov
Department of Genetics, University of Groningen, University Medical Center Groningen, 9713 EX Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Centre Groningen, 9713 EX Groningen, the Netherlands.
Jingyuan
J
Fu
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, 6525 GA Nijmegen, the Netherlands.
Leo A B
LAB
Joosten
Department of Genetics, University of Groningen, University Medical Center Groningen, 9713 EX Groningen, the Netherlands.
Alexandra
A
Zhernakova
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Curtis
C
Huttenhower
Department of Genetics, University of Groningen, University Medical Center Groningen, 9713 EX Groningen, the Netherlands.
Cisca
C
Wijmenga
Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboudumc, 6525 GA Nijmegen, the Netherlands. Electronic address: mihai.netea@radboudumc.nl.
Mihai G
MG
Netea
The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
Ramnik J
RJ
Xavier
D000293:Adolescent; D000328:Adult; D000368:Aged; D001419:Bacteria / Q000145:classification / Q000276:immunology; D001769:Blood / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D064806:Dysbiosis / Q000276:immunology / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D005658:Fungi / Q000145:classification / Q000276:immunology; D000069196:Gastrointestinal Microbiome; D059647:Gene-Environment Interaction; D016045:Human Genome Project; D006801:Humans; D007239:Infections / Q000276:immunology / Q000382:microbiology; D007249:Inflammation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D064307:Microbiota; D008875:Middle Aged
D016207:Cytokines
Human Functional Genomics Project; database of microbiome-cytokine associations; healthy human cohort; human gut microbiome; immunological profiles; inflammatory cytokine response; interindividual variation; metagenomics; microbial profiles; microbiome-host interactions