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Recent advances in basic science
Gut microbiome and health: mechanistic insights
  1. Willem M de Vos1,2,
  2. Herbert Tilg3,
  3. Matthias Van Hul4,
  4. Patrice D Cani4
  1. 1 Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  2. 2 Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
  3. 3 Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
  4. 4 Louvain Drug Research Institute (LDRI), Metabolism and Nutrition research group (MNUT), UCLouvain, Université catholique de Louvain, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), Brussels, Belgium
  1. Correspondence to Professor Patrice D Cani, Louvain Drug Research Institute, WELBIO, Metabolism and Nutrition, UCLouvain, Université catholique de Louvain, Brussels, Belgium; patrice.cani{at}uclouvain.be

Abstract

The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metabolism are affected.

In this review, specific attention is given to provide a critical evaluation of the current understanding in this field. Numerous molecular mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, short-chain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified molecular actors (ie, endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5).

Altogether, understanding the complexity and the molecular aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.

  • intestinal microbiology
  • obesity
  • intestinal barrier function
  • liver
  • probiotics
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/gutjnl-2021-326789

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    Footnotes

    • Twitter @matthias_vanhul, @MicrObesity

    • WMdV, HT, MVH and PDC contributed equally.

    • Correction notice This article has been corrected since it published Online First. Figure 3 has been enlarged.

    • Contributors PDC has prepared a proposal on the conception of the overall content of the manuscript. PDC, HT, WMdV and MVH have revised, amended and approved the proposal. PDC, HT, WMdV and MVH have collected content, selected the key references, written and critically reviewed the content of the manuscript. PDC and MVH have prepared the figures. PDC, HT, WMdV and MVH have all revised the final version of the manuscript. PDC, HT, WMdV and MVH contributed equally to this paper.

    • Funding PDC is research director at FRS-FNRS (Fonds de la Recherche Scientifique) and the recipient of grants from FNRS (Projet de Recherche PDR-convention: FNRS T.0030.21, CDR-convention: J.0027.22, FRFS-WELBIO: WELBIO-CR-2017C-02E, WELBIO-CR-2019C-02R, EOS: program no. 30770923 and EOS program no. 40007505). WMDV was supported by the SIAM Gravitation Grant (024.002.002) of the Netherlands Organization for Scientific Research. HT is supported by the excellence initiative VASCage (Centre for Promoting Vascular Health in the Ageing Community), an R&D K-Centre (COMET program—Competence Centers for Excellent Technologies) funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol, Salzburg and Vienna.

    • Competing interests PDC and WMdV are inventors on patent applications dealing with the use of Akkermansia muciniphila and its components in the treatment of metabolic disorders. PDC and WMdV are co-founders of A-Mansia Biotech. PDC is co-founder of Enterosys. WMdV is co-founder of Caelus Health and inventor on patents on the use of Eubacterium hallii.

    • Provenance and peer review Commissioned; internally peer reviewed.