Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

Melanie Schirmer, Sanne P. Smeekens, Hera Vlamakis, Martin Jaeger, Marije Oosting, Eric A. Franzosa, Rob ter Horst, Trees Jansen, Liesbeth Jacobs, Marc Jan Bonder, Aleksandr Kurilshchikov, Jingyuan Fu, Leo A. B. Joosten, Alexandra Zhernakova, Curtis Huttenhower, Cisca Wijmenga, Mihai G. Netea, Ramnik J. Xavier

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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 TNF alpha and IFN gamma 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.

Original languageEnglish
Pages (from-to)1125-1136
Number of pages12
JournalCell
Volume167
Issue number4
DOIs
Publication statusPublished - 3-Nov-2016

Keywords

  • CANDIDA-ALBICANS
  • CARDIOVASCULAR-DISEASE
  • RHEUMATOID-ARTHRITIS
  • IMMUNE-RESPONSE
  • FATTY-ACIDS
  • METABOLITES
  • TRYPTOPHAN
  • COLITIS
  • BLOOD
  • SUSCEPTIBILITY

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