Research output: Contribution to journal › Article › peer-review
Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity. / Schirmer, Melanie; Smeekens, Sanne P.; Vlamakis, Hera et al.
In: Cell, Vol. 167, No. 4, 03.11.2016, p. 1125-1136.e8.Research output: Contribution to journal › Article › peer-review
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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 -
ID: 34659101