Dietary metabolism, the gut microbiome, and heart failure

Abstract

Advances in our understanding of how the gut microbiota contributes to human health and diseases have expanded our insight into how microbial composition and function affect the human host. Heart failure is associated with splanchnic circulation congestion, leading to bowel wall oedema and impaired intestinal barrier function. This situation is thought to heighten the overall inflammatory state via increased bacterial translocation and the presence of bacterial products in the systemic blood circulation. Several metabolites produced by gut microorganisms from dietary metabolism have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. These findings suggest that the gut microbiome functions like an endocrine organ by generating bioactive metabolites that can directly or indirectly affect host physiology. In this Review, we discuss several newly discovered gut microbial metabolic pathways, including the production of trimethylamine and trimethylamine N-oxide, short-chain fatty acids, and secondary bile acids, that seem to participate in the development and progression of cardiovascular diseases, including heart failure. We also discuss the gut microbiome as a novel therapeutic target for the treatment of cardiovascular disease, and potential strategies for targeting intestinal microbial processes.

Key points

  • The gut hypothesis of heart failure (HF) postulates that bowel wall oedema and impaired intestinal barrier function in HF can promote bacterial translocation and inflammation.

  • Changes in the composition and diversity of the gut microbiota have been observed in patients with HF.

  • Microbial metabolites, especially those derived from dietary nutrients, can generate paracrine and endocrine effects that can lead to an increased susceptibility to HF.

  • Novel therapeutic strategies targeting gut microbial metabolic pathways and/or metabolites, as well as altering gut microbial composition, have the potential to modulate cardiovascular disease susceptibility and prevent progression to HF.

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Fig. 1: Microbial–host meta-organismal pathway linking dietary metabolism, the gut microbiota, and cardiorenal disease progression.
Fig. 2: Downstream effects of gut microbiota-generated short-chain fatty acids in the cardiovascular system.
Fig. 3: Microbial generation of dietary-induced trimethylamine and trimethylamine N-oxide.
Fig. 4: Relationship between plasma levels of trimethylamine N-oxide and 5-year risk of death in patients with chronic heart failure.
Fig. 5: Microbial metabolic pathways as potential druggable targets.

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Acknowledgements

The authors’ research work is supported by grants from the National Institutes of Health (NIH) and the Office of Dietary Supplements, including R01HL103866 (S.L.H.), and P20HL113452, R01DK106000, and R01HL126827 (W.H.W.T. and S.L.H.).

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W.H.W.T. and D.Y.L. researched data for the article, and all authors discussed its content. W.H.W.T. and D.Y.L. wrote the manuscript, and W.H.W.T. and S.L.H. reviewed and edited it before submission.

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Correspondence to W. H. Wilson Tang.

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S.L.H. is named as a co-inventor on pending and issued patents held by the Cleveland Clinic, USA, relating to cardiovascular diagnostics and therapeutics; he is a paid consultant for Proctor & Gamble and has received research funds from Proctor & Gamble and Roche Diagnostics; and he is eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland Heart Lab/Quest Diagnostics or Proctor & Gamble. The other authors declare no competing interests.

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NIH Human Microbiome Project: https://hmpdacc.org/

Metagenomics of the Human Intestinal Tract (MetaHIT): http://www.metahit.eu/

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Meta-organismal

Relating to a polygenomic organism consisting of a community of living beings of different species (such as microbiota and host) associated by interspecies symbiosis.

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Tang, W.H.W., Li, D.Y. & Hazen, S.L. Dietary metabolism, the gut microbiome, and heart failure. Nat Rev Cardiol 16, 137–154 (2019). https://doi.org/10.1038/s41569-018-0108-7

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