Microbiome-Modulated Metabolites at the Interface of Host Immunity [BRIEF REVIEWS]

Abstract

The mammalian gastrointestinal tract and associated mucosal immune system harbor a large repertoire of metabolites of prokaryotic and eukaryotic origin that play important roles in eukaryotic development and physiology. These often bioactive small molecules originate from nutrition- and environmental-related sources, or are endogenously produced and modulated by the host and its microbiota. A complex network of interactions exists between the intestinal mucosal immune system and the microbiota. This intimate cross-talk may be driven by metabolite secretion and signaling, and features profound influences on host immunity and physiology, including the endocrine, metabolic, and nervous system function in health and disease. Alterations in microbiome-associated metabolite levels and activity are implicated in the pathogenesis of a growing number of illnesses. In this review we discuss the origin and influence of microbiome-modulated metabolites, with an emphasis on immune cell development and function. We further highlight the emerging data potentially implicating metabolite misbalance with host-microbiome–associated disease.

Footnotes

  • E.E. was supported by Y. and R. Ungar, the Abisch Frenkel Foundation for the Promotion of Life Sciences, the Gurwin Family Fund for Scientific Research, the Leona M. and Harry B. Helmsley Charitable Trust, the Crown Endowment Fund for Immunological Research, the estate of J. Gitlitz, the estate of L. Hershkovich, the Benoziyo Endowment Fund for the Advancement of Science, the Adelis Foundation, J.L. and V. Schwartz, A. and G. Markovitz, A. and C. Adelson, the French National Center for Scientific Research, D.L. Schwarz, the V.R. Schwartz Research Fellow Chair, L. Steinberg, J.N. Halpern, A. Edelheit, grants funded by the European Research Council, a Marie Curie Career Integration grant, the German–Israeli Foundation for Scientific Research and Development, the Israel Science Foundation, the Minerva Foundation, the Rising Tide Foundation, the Helmholtz Association, and the European Foundation for the Study of Diabetes. E.E. is the incumbent Rina Gudinski Career Development Chair and is a senior fellow at the Canadian Institute for Advanced Research.

  • Abbreviations used in this article:

    AHR
    aryl hydrocarbon receptor
    ASD
    autistic spectrum disorder
    BBB
    blood–brain barrier
    DC
    dendritic cell
    FXR
    farnesoid X receptor
    HDAC
    histone deacetylase
    IBD
    inflammatory bowel disease
    IEC
    intestinal epithelial cell
    ILC
    innate lymphoid cell
    NA
    nicotinic acid
    NAFLD
    nonalcoholic fatty liver disease
    NASH
    nonalcoholic steatohepatitis
    SCFA
    short chain fatty acid
    SFB
    segmented filamentous bacteria
    TMAO
    trimethylamine-N-oxide
    Treg
    regulatory T cell
    Trp
    tryptophan
    WT
    wild type.
  • Received July 18, 2016.
  • Accepted October 13, 2016.

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