Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer

Abstract

Overweight and obesity are associated with increased risk of developing metabolic disorders such as diabetes and cardiovascular diseases. However, besides these metabolic diseases, excess body weight is also associated with different cancers, including gastrointestinal cancers, such as liver, pancreatic and colon cancers. Inflammation is a common feature of both obesity and cancer; however, the origin of this inflammation has been largely debated. Over the past decade, growing evidence has shown that the composition of the gut microbiota and its activity might be associated not only with the onset of inflammation but also with metabolic disorders and cancer. Here, we review the links between the gut microbiota, gut barrier function and the onset of low-grade inflammation in the development of gastrointestinal cancer. We also describe the mechanisms by which specific microorganism-associated molecular patterns crosstalk with the immune system and how the metabolic activity of bacteria induces specific signalling pathways beyond the gut that eventually trigger carcinogenesis.

Key points

  • Gut microorganisms produce a myriad of metabolites and factors that affect host metabolism and immunity.

  • Obesity and gastrointestinal cancer are characterized by inflammation and common molecular mechanisms contributing to the onset of these diseases.

  • Specific gut bacteria are undeniably associated with the development of gastrointestinal cancers.

  • Targeting the composition of the intestinal microbiota and eventually the metabolites produced might constitute an interesting strategy to tackle obesity and cancers.

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Fig. 1: Production of active metabolites by the gut microbial factory.
Fig. 2: Gut barrier dysfunction and low-grade inflammation in obesity and cancer.
Fig. 3: Mechanisms by which obesity-related inflammation and microbial metabolites modulate gastrointestinal cancer.

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Acknowledgements

B.F.J. and P.D.C. are senior research associates at FRS-FNRS (Fonds de la Recherche Scientifique). P.D.C. is a recipient of grants from FNRS (Projet de Recherche, convention: T.0138.14) and Walloon region DG06-FSO project (Microbes 1510053). This work was supported by FRFS-WELBIO (Fund for Strategic Fundamental Research-Walloon Excellence in Life sciences and Biotechnology) grants, WELBIO-CR-2012S-02 R and WELBIO-CR-2017-C02 (continuation grant 2017), and in part by the Fonds Baillet Latour (Grant for Medical Research 2015). P.D.C. is a recipient of Proof of Concept ERC grant 2016 (European Research Council, Microbes4U_713547) and ERC Starting Grant 2013 (Starting grant 336452-ENIGMO).

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P.D.C. is inventor on patent applications dealing with the use of Akkermansia muciniphila and its components in the treatment of obesity and related disorders. P.D.C. is co-founder of A-Mansia biotech SA. B.F.J. declares no competing interests.

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Cani, P.D., Jordan, B.F. Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer. Nat Rev Gastroenterol Hepatol 15, 671–682 (2018). https://doi.org/10.1038/s41575-018-0025-6

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