Metabolites: Messengers Between the Microbiota and the Immune System

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2016 Jul 31

PMID 27474437

Citations 214

Authors

Maayan Levy

Christoph A Thaiss

Eran Elinav

Affiliations

Soon will be listed here.

Abstract

The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases.

Citing Articles

Influence of gut microbial metabolites on tumor immunotherapy: mechanisms and potential natural products.

Li D, Lan X, Xu L, Zhou S, Luo H, Zhang X Front Immunol. 2025; 16:1552010.

PMID: 40066456 PMC: 11891355. DOI: 10.3389/fimmu.2025.1552010.

Deciphering the coordinated roles of the host genome, duodenal mucosal genes, and microbiota in regulating complex traits in chickens.

Lan F, Wang X, Zhou Q, Li X, Jin J, Zhang W Microbiome. 2025; 13(1):62.

PMID: 40025569 PMC: 11871680. DOI: 10.1186/s40168-025-02054-5.

Atg5 deficiency in basophils improves metabolism in lupus mice by regulating gut microbiota dysbiosis.

Chen J, Pan Q, Lu L, Huang X, Wang S, Liu X Cell Commun Signal. 2025; 23(1):40.

PMID: 39844180 PMC: 11756211. DOI: 10.1186/s12964-025-02041-1.

Converging frontiers in cancer treatment: the role of nanomaterials, mesenchymal stem cells, and microbial agents-challenges and limitations.

Afkhami H, Yarahmadi A, Bostani S, Yarian N, Haddad M, Lesani S Discov Oncol. 2024; 15(1):818.

PMID: 39707033 PMC: 11662135. DOI: 10.1007/s12672-024-01590-0.

Relevance of Indian Traditional Herbal Brews for Gut Microbiota Balance.

Joshi D, Deb L, Kaul K, Somkuwar B, Rana V, Singh R Indian J Microbiol. 2024; 64(4):1425-1444.

PMID: 39678955 PMC: 11645388. DOI: 10.1007/s12088-024-01251-4.

References

Maslowski K, Vieira A, Ng A, Kranich J, Sierro F, Yu D . Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009; 461(7268):1282-6. PMC: 3256734. DOI: 10.1038/nature08530. View

Romani L, Fallarino F, De Luca A, Montagnoli C, DAngelo C, Zelante T . Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature. 2008; 451(7175):211-5. DOI: 10.1038/nature06471. View

Furusawa Y, Obata Y, Fukuda S, Endo T, Nakato G, Takahashi D . Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013; 504(7480):446-50. DOI: 10.1038/nature12721. View

Hoverstad T, Midtvedt T . Short-chain fatty acids in germfree mice and rats. J Nutr. 1986; 116(9):1772-6. DOI: 10.1093/jn/116.9.1772. View

Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M . Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science. 2007; 317(5835):256-60. DOI: 10.1126/science.1145697. View

Round J, Mazmanian S . Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A. 2010; 107(27):12204-9. PMC: 2901479. DOI: 10.1073/pnas.0909122107. View

Martens J, Barg H, Warren M, Jahn D . Microbial production of vitamin B12. Appl Microbiol Biotechnol. 2002; 58(3):275-85. DOI: 10.1007/s00253-001-0902-7. View

Murray P . Amino acid auxotrophy as a system of immunological control nodes. Nat Immunol. 2016; 17(2):132-9. PMC: 4893777. DOI: 10.1038/ni.3323. View

Trompette A, Gollwitzer E, Yadava K, Sichelstiel A, Sprenger N, Ngom-Bru C . Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med. 2014; 20(2):159-66. DOI: 10.1038/nm.3444. View

10.

Fischbach M, Sonnenburg J . Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe. 2011; 10(4):336-47. PMC: 3225337. DOI: 10.1016/j.chom.2011.10.002. View

11.

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View

12.

Nicholson J, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W . Host-gut microbiota metabolic interactions. Science. 2012; 336(6086):1262-7. DOI: 10.1126/science.1223813. View

13.

Spencer S, Wilhelm C, Yang Q, Hall J, Bouladoux N, Boyd A . Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science. 2014; 343(6169):432-7. PMC: 4313730. DOI: 10.1126/science.1247606. View

14.

Sun C, Hall J, Blank R, Bouladoux N, Oukka M, Rodrigo Mora J . Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med. 2007; 204(8):1775-85. PMC: 2118682. DOI: 10.1084/jem.20070602. View

15.

Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P . Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013; 504(7480):451-5. PMC: 3869884. DOI: 10.1038/nature12726. View

16.

Morrison D, Preston T . Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016; 7(3):189-200. PMC: 4939913. DOI: 10.1080/19490976.2015.1134082. View

17.

Qiu J, Heller J, Guo X, Chen Z, Fish K, Fu Y . The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity. 2011; 36(1):92-104. PMC: 3268875. DOI: 10.1016/j.immuni.2011.11.011. View

18.

Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal W, Strowig T . Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012; 482(7384):179-85. PMC: 3276682. DOI: 10.1038/nature10809. View

19.

Hall J, Cannons J, Grainger J, Dos Santos L, Hand T, Naik S . Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity. 2011; 34(3):435-47. PMC: 3415227. DOI: 10.1016/j.immuni.2011.03.003. View

20.

Alex S, Lange K, Amolo T, Grinstead J, Haakonsson A, Szalowska E . Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ. Mol Cell Biol. 2013; 33(7):1303-16. PMC: 3624264. DOI: 10.1128/MCB.00858-12. View