Review

Gut microbiota, metabolites and host immunity

  • Nature Reviews Immunology 16, 341352 (2016)
  • doi:10.1038/nri.2016.42
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Abstract

The microbiota — the collection of microorganisms that live within and on all mammals — provides crucial signals for the development and function of the immune system. Increased availability of technologies that profile microbial communities is facilitating the entry of many immunologists into the evolving field of host–microbiota studies. The microbial communities, their metabolites and components are not only necessary for immune homeostasis, they also influence the susceptibility of the host to many immune-mediated diseases and disorders. In this Review, we discuss technological and computational approaches for investigating the microbiome, as well as recent advances in our understanding of host immunity and microbial mutualism with a focus on specific microbial metabolites, bacterial components and the immune system.

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Acknowledgements

The authors thank the members of the Garrett laboratory for their helpful discussions. The work relevant to this Review is supported by the grants R01 CA154426 and R01 GM099531, a Burroughs Wellcome Career in Medical Sciences Award and a Searle Scholars Award to W.S.G.

Author information

Affiliations

  1. Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA.

    • Michelle G. Rooks
    •  & Wendy S. Garrett
  2. Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Wendy S. Garrett
  3. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.

    • Wendy S. Garrett
  4. Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

    • Wendy S. Garrett

Authors

  1. Search for Michelle G. Rooks in:

  2. Search for Wendy S. Garrett in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Wendy S. Garrett.

Glossary

Dysbiosis

An imbalance in the composition or function of the microbial species that are normally found in mammalian hosts. It is associated with alterations in immune function and susceptibility to inflammatory diseases, allergies and metabolic conditions.

Gnotobiotic mouse models

Experimental models in which germ-free mice are selectively colonized by defined microorganisms and kept in isolators to control their microbial colonization status.

Bone marrow–liver–thymus humanized mice

(BLT humanized mice). Immunodeficient mice that are engrafted with human fetal liver and thymus under the renal capsule. Three weeks later, mice are irradiated and then injected with a suspension of CD34+ cells from the same human fetal liver sample. These fetal liver cells seed to the mouse bone marrow.

Humanized mouse models

Experimental models in which mice carry functioning human genes, cells, tissues (including faecal material) or organs that are introduced by transgenesis, injection or transplantation. For example, an immunodeficient mouse transgenically expressing susceptibility genes for type 1 diabetes and reconstituted with T cells from a patient with type 1 diabetes and human islets of Langerhans can be used to study relevant autoimmune processes.

Fluorescence in situ hybridization

(FISH). A technique in which fluorescent probes are used to visually label specific DNA sequences in the nuclei of cells.

Metabolic oligosaccharide engineering

(MOE). A technology in which synthetic sugar analogues are exogenously supplied to living cells and biosynthetically incorporated into cell surface polysaccharides. An advantage of this technology is that it can be used for prokaryotic and eukaryotic cells that are grown under aerobic or anaerobic conditions.

Bio-orthogonal click chemistry

(BCC). A chemical reaction in a living cell that allows a labelled synthetic probe to be covalently linked to targeted cellular substrates without disrupting any native functions of the cell. This method can be used to tag and visualize biomolecules within cells of interest.

Anaerobic fermentation

The process of extracting energy from carbohydrates. Some bacteria are facultative anaerobes, meaning they can switch between aerobic respiration and anaerobic pathways, depending on the availability of oxygen or other electron acceptors. Other bacteria are obligate anaerobes, meaning they completely rely on anaerobic fermentation and can only survive in the absence of oxygen.

Histone deacetylases

(HDACs). Enzymes that remove the acetyl groups from lysine residues that are located at the amino termini of histones. In general, decreased levels of histone acetylation are associated with the repression of gene expression. The balance of histone acetylation is maintained by the interplay between HDACs and histone acetyltransferases.

Dextran sodium sulfate-induced injury model

(DSS-induced injury model). A commonly used experimental model of colonic injury and mucosal inflammation induced in mice by ingestion of the sulfated polysaccharide DSS. This model causes acute colonic epithelial damage and inflammation.

T cell transfer colitis model

A well-characterized model of chronic colitis that is induced by the transfer of CD4+CD45RBhi (naive) T cells from healthy wild-type mice into immunodeficient syngeneic recipients.

Xenobiotics

Compounds inclusive of drugs, food components and pollutants.

Innate lymphoid cell

(ILC). A lymphoid cell that is derived from the common lymphoid progenitor and does not express a recombined antigen receptor. ILCs have important roles in innate immune responses to infectious microorganisms, in epithelial homeostasis and in lymphoid tissue formation.