A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile acids, or directly from bacteria. Signals from microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity. Alterations in the composition and function of the microbiota have been described in many studies on IBD. Alterations have also been described in the metabolite profiles of patients with IBD. Furthermore, specific classes of metabolites, notably bile acids, short-chain fatty acids and tryptophan metabolites, have been implicated in the pathogenesis of IBD. This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.
IBD, which includes Crohn’s disease and ulcerative colitis, is a set of clinically important, chronic inflammatory conditions of the gastrointestinal tract in which altered host processing of gut microbiota-derived signals, in addition to altered composition and function of the gut microbiota, have been strongly implicated.
Gut microbiota-derived metabolites are key molecular mediators between the microbiota and host.
Several untargeted studies have demonstrated broad disturbances of the gut metabolome in IBD, which is in keeping with the known dysbiosis in gut communities.
Metabolite groups of interest include short-chain fatty acids, bile acid metabolites and tryptophan metabolites, with essential roles for these metabolites in normal immune development, homeostasis and IBD.
Multinational, longitudinal cohorts, multi-omics characterization, sampling and analysis standardization and model systems will be required to expand our knowledge of these associations.
Such approaches show promise for identifying new host targets and the microbial tools with which to target them.
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A.L. has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. PCOFUND-GA-2013-609102, through the PRESTIGE programme coordinated by Campus France. H.S. received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (ERC-2016-StG-71577).
H.S. has received unrestricted study grants from Danone, Biocodex and Enterome; board membership, consultancy, or lecture fees from Carenity, Abbvie, Astellas, Danone, Ferring, Mayoly Spindler, MSD, Novartis, Roche, Tillots, Enterome, Maat, BiomX, Biose, Novartis and Takeda; and is a cofounder of Exeliom Biosciences. A.L. declares no competing interests.
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Lavelle, A., Sokol, H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 17, 223–237 (2020). https://doi.org/10.1038/s41575-019-0258-z