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Unveiling the role of gut microbiota in cardiovascular diseases: new pieces to the puzzle

Paper commented by the ESC Working Group on Cellular Biology of the Heart

Atherosclerosis, Cerebrovascular Diseases, Aneurysm, Restenosis
Leukocytes, Inflammation, Immunity
Basic Science
Vascular Biology and Physiology
Vascular Diseases


Compelling evidence now indicates that gut microbiota can influence host cardiovascular health and disease, since modulation of gut microbiota composition and function may alter host profile in favorable/unfavorable fashion (1). In particular, evidence that high circulating levels of the microbiota-generated metabolite trimethyl-amine-N-oxide (TMAO) are linked to an increased risk of atherosclerosis and cardiovascular risk is now solid (2-3).

In a recent issue of Circulation Research, Brandsma et al, add new pieces to this intricate puzzle. Here the Authors show that transplantation of gut microbiota from Casp1-/- mice induces inflammation and atherosclerosis in antibiotic-treated Ldlr -/- mice fed with a high-fat cholesterol-rich diet, establishing a causal relationship between microbiota composition, inflammation and atherosclerosis independent of plasma lipids, gut integrity and TMAO levels (4).

This important and interesting work raises several questions for future research. Further investigations will be required to define the fingerprint of a “healthy” microbiota, and to identify microbial metabolites mediating the crosstalk between host and bacteria, to be used as novel biomarkers and/or potential pharmacological targets (5). Only few studies have provided so far a mechanistic link between specific bacterial species and the monitored phenotype.

Moreover, multiple discrepancies can still be noted when comparing major bacterial groups identified in different studies, raising reproducibility concerns, considering also that microbe-microbe interactions might represent an additional knowledge gap. Finally, confounding effects related to environment, comorbidities, treatments and “reverse” effects of microbiota on drug metabolism should be taken into account when translating such preclinical observations to the clinical arena.

References


  1. Schiattarella GG, Sannino A, Esposito G, Perrino C. Diagnostics and therapeutic implications of gut microbiota alterations in cardiometabolic diseases. Trends Cardiovasc Med. 2018 Aug 7. pii: S1050-1738(18)30155-5. doi: 10.1016/j.tcm.2018.08.003.
  2. Schiattarella GG, Sannino A, Toscano E, Giugliano G, Gargiulo G, Franzone A, Trimarco B, Esposito G, Perrino C.Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis. Eur Heart J. 2017 Oct 14;38(39):2948-2956. doi: 10.1093/eurheartj/ehx342.
  3. Wang Z1, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922.
  4. Brandsma E, Kloosterhuis NJ, Koster M, Dekker DC, Gijbels MJJ, van der Velden S, Ríos-Morales M, van Faassen MJR, Loreti MG, de Bruin A, Fu J, Kuipers F, Bakker BM, Westerterp M, de Winther MPJ, Hofker MH, van de Sluis B, Koonen DPY. A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis. Circ Res. 2019 Jan 4;124(1):94-100. doi:10.1161/CIRCRESAHA.118.313234.
  5. Dekker Nitert M. Knights in Shining Armor. Circ Res. 2019 Jan 4;124(1):12-14. doi: 10.1161/CIRCRESAHA.118.314246.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.