The gut microbiome has emerged as a key regulator of host metabolism. Here we review the various mechanisms through which the gut microbiome influences the energy metabolism of its host, highlighting the complex interactions between gut microbes, their metabolites and host cells. Among the most important bacterial metabolites are short-chain fatty acids, which serve as a direct energy source for host cells, stimulate the production of gut hormones and act in the brain to regulate food intake. Other microbial metabolites affect systemic energy expenditure by influencing thermogenesis and adipose tissue browning. Both direct and indirect mechanisms of action are known for specific metabolites, such as bile acids, branched chain amino acids, indole propionic acid and endocannabinoids. We also discuss the roles of specific bacteria in the production of specific metabolites and explore how external factors, such as antibiotics and exercise, affect the microbiome and thereby energy homeostasis. Collectively, we present a large body of evidence supporting the concept that gut microbiota-based therapies can be used to modulate host metabolism, and we expect to see such approaches moving from bench to bedside in the near future.
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P.D.C. is a senior research associate at FRS-FNRS (Fonds de la Recherche Scientifique). A.E. is a research associate and MR research fellow at the FRS-FNRS. P.D.C. is a recipient of grants from FNRS, FRFS-WELBIO, under grant no. WELBIO-CR-2017-C02. This research was supported by the FRS-FNRS under The Excellence Of Science (EOS 30770923). This work is supported in part by the Funds Baillet Latour (Grant for Medical Research 2015). P.D.C. is a recipient of the POC ERC grant 2016 (European Research Council, Microbes4U_713547) and ERC Starting Grant 2013 (Starting grant 336452-ENIGMO).
P.D.C. and A.E. are inventors on patent applications (PCT/EP2013/073972; PCT/EP2016/071327, PCT/EP2016/060033 filed in European Patent Office (EP), Australia (AU), Brazil (BR), Canada (CA), China (CN), Eurasian Patent Organization (EA), Israel (IL), India (IN), Hong Kong (HK), Japan (JP), South Korea (KR), Mexico (MX), New Zealand (NZ), and the United States (US)) about the therapeutic use of A. muciniphila and its components. P.D.C. is co-founder of A-Mansia biotech SA.
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Cani, P.D., Van Hul, M., Lefort, C. et al. Microbial regulation of organismal energy homeostasis. Nat Metab 1, 34–46 (2019). https://doi.org/10.1038/s42255-018-0017-4
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