TY - JOUR

T1 - Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

AU - Schirmer, Melanie

AU - Smeekens, Sanne P.

AU - Vlamakis, Hera

AU - Jaeger, Martin

AU - Oosting, Marije

AU - Franzosa, Eric A.

AU - Jansen, Trees

AU - Jacobs, Liesbeth

AU - Bonder, Marc Jan

AU - Kurilshikov, Alexander

AU - Fu, Jingyuan

AU - Joosten, Leo A.B.

AU - Zhernakova, Alexandra

AU - Huttenhower, Curtis

AU - Wijmenga, Cisca

AU - Netea, Mihai G.

AU - Xavier, Ramnik J.

N1 - Funding Information: The authors thank all volunteers from the 500FG cohort for participating. The HFGP is supported by grants to M.G.N. ( ERC Consolidator Grant [ 3310372 ], Spinoza Prize [ NOW SPI 94-212 ], and IN-CONTROL CVON grant [CVON 2012-03]) and C.W. ( ERC Advanced Grant [ FP/2007-2013/ERC grant 2012-322698 ], Spinoza Prize [ NWO SPI 92-266 ], the Dutch Digestive Diseases Foundation [ MLDS WO11-30 ], and the European Union’s Seventh Framework Programme [ EU FP7 ] TANDEM project [ HEALTH-F3-2012-305279 ]). R.J.X. was supported by grants from NIH ( U54DK102557 and R01DK092405 ), Helmsley Charitable Trust (2014PG-IBD016), JDRF ( 17-2011-529 ), and CCFA ( 20144126 ). A.Z., J.F., and A.K. were supported by a CVON grant (CVON 2012-03). S.P.S. was financially supported by STW grant STW13546 . A.Z. holds a Rosalind Franklin Fellowship ( University of Groningen ). J.F. is funded by the Netherlands Organisation for Scientific Research ( NWO-VIDI 864.13.013 ). We thank Tiffany Poon for help in sequence production and sample management and Natalia Nedelsky (Massachusetts General Hospital) for editorial help and help with figure generation. We also thank Edith Adriaanse, Marije van der Geest, and Marieke Bijlsma for structuring the online database and the MOLGENIS open source team, Dennis Hendriksen, Erwin Winder, Bart Charbon, Fleur Kelpin, Jonathan Jetten, Mark de Haan, Tommy de Boer, David van Enckevort, Chao Pang, Joeri van der Velde, and Morris Swertz for designing and implementing the database software. The creation and hosting of the online database was supported by BBMRI-NL, a research infrastructure financed by the Netherlands Organisation for Scientific Research (NWO), grant number 184.021.007 . We thank Maria Carmen Cenit, Astrid Maatman, Mathieu Plateel, and Jody Arends for technical support, and Daniel Graham for helpful advice and discussions. We also thank https://thenounproject.com for providing the figure icons “Male Aging”/”Female Aging” by Marie Van den Broeck. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/11/3

Y1 - 2016/11/3

N2 - 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

AB - 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

KW - database of microbiome-cytokine associations

KW - healthy human cohort

KW - Human Functional Genomics Project

KW - human gut microbiome

KW - immunological profiles

KW - inflammatory cytokine response

KW - interindividual variation

KW - metagenomics

KW - microbial profiles

KW - microbiome-host interactions

UR - http://www.scopus.com/inward/record.url?scp=84994738020&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2016.10.020

DO - 10.1016/j.cell.2016.10.020

M3 - Article

C2 - 27814509

AN - SCOPUS:84994738020

VL - 167

SP - 1125-1136.e8

JO - Cell

JF - Cell

SN - 0092-8674

IS - 4

ER -