Resveratrol Attenuates Atherosclerosis Through Actions on Gut Microbiome

MedicalResearch.com Interview with:
Man-tian Mi

Research Center for Nutrition and Food Safety,
Chongqing Key Laboratory of Nutrition and Food Safety,
Institute of Military Preventive Medicine,
Third Military Medical University
Chongqing  China 

MedicalResearch.com: What is the background for this study? What are the main findings?

Reply: Cardiovascular diseases remain the leading cause of death in industrialized societies including the United States, and the incidence is growing in developing countries (1). In recent years, researchers have learned that the gut microbiome plays a role in the build up of plaque inside arteries, otherwise known as atherosclerosis (2, 3). Resveratrol, a polyphenol found in red wine, is thought to have antioxidant properties that protect against conditions such as heart disease (4). Just how resveratrol, a plant compound, does this, however, is unclear. Therefore, we sought to determine whether the anti-atherosclerosis effects of resveratrol were related to changes in the gut microbiota.

We found that resveratrol attenuated trimethylamine-N-oxide (TMAO)-induced  atherosclerosis by decreasing TMAO levels and increasing hepatic bile acid (BA) neosynthesis via gut microbiota remodeling, and the BA neosynthesis was partially mediated through the enterohepatic farnesoid X receptor-fibroblast growth factor 15 axis. These results offer new insights into the mechanisms responsible for resveratrol’s anti-atherosclerosis effects and indicate that gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing cardiovascular diseases.

MedicalResearch.com: What should clinicians and patients take away from your report?

Reply: The incidence of cardiovascular diseases, such as atherosclerosis, is increasing globally and has become an expensive public health issue (1). Our results indicate that gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing cardiovascular diseases. This will provide a new way to treat cardiovascular diseases patients. After examing the community of their gut microbiota, the cardiovascular diseases patients can choose some probiotic or prebiotic to exactly remodel their gut microbiota to keep themselves far away from developing cardiovascular diseases. Moreover, our findings might explain the paradox that resveratrol has low bioavailability in humans, while exerting noticeable bioactivities, which is a major concern for the development of this class of compounds into therapeutic agents (5, 6). It is good news for cardiovascular diseases patients that resveratrol, a natural polyphenol without any side effects, might function as a prebioitc and will be widely used as an effective agent for them clinically in the near future.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Reply: In our current study, we found that resveratrol decreased TMAO levels by inhibiting gut microbial trimethylamine (TMA) production via gut microbiota remodeling. However, we failed to provide exact data about the effect of resveratrol on the abundance of functional genes related to TMA formation (cutC, cutD or other TMA lyases) (7, 8). Therefore, first of all, future research can clarify the core microbiota regulated by resveratrol and the effect of resveratrol on microbial TMA lyase (cutC, cutD or other TMA lyases). Moreover, there are certainly many differences between animals and humans. In our present study, we just proved mechanistically in mice that resveratrol attenuated TMAO-induce atherosclerosis by regulating TMAO and bile acid metabolism via remodeling of the gut microbiota. Thus, to further confirm these results in humans is one of the next valuable works. These works will provide meaningful evidence for using resveratrol as a selective microbial TMA lyase inhibitor to non-lethally inhibit gut microbial TMA production for the treatment of atherosclerosis.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

References:

  1. Murray CJ, Lopez AD. 1997. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 349:1498-1504.
  2. Wang Z, 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. 2011. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57-63.
  3. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. 2013. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 368:1575-1584.
  4. Chung JH, Manganiello V, Dyck JRB. 2012. Resveratrol as a calorie restriction mimetic: therapeutic implications. Trends in Cell Biology 22:546-554.
  5. Subramanian L, Youssef S, Bhattacharya S, Kenealey J, Polans AS, van Ginkel PR. 2010. Resveratrol: Challenges in Translation to the Clinic – A Critical Discussion. Clinical Cancer Research 16:5942-5948.
  6. Asensi M, Medina I, Ortega A, Carretero J, Bano MC, Obrador E, Estrela JM. 2002. Inhibition of cancer growth by resveratrol is related to its low bioavailability. Free Radic Biol Med 33:387-398.
  7. Bennett BJ, Vallim TQD, Wang ZN, Shih DM, Meng YH, Gregory J, Allayee H, Lee R, Graham M, Crooke R, Edwards PA, Hazen SL, Lusis AJ. 2013. Trimethylamine-N-Oxide, a Metabolite Associated with Atherosclerosis, Exhibits Complex Genetic and Dietary Regulation. Cell Metabolism 17:49-60.
  8. Romano KA, Vivas EI, Amador-Noguez D, Rey FE. 2015. Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide. Mbio 6.

Citation:

Ming-liang Chen, Long Yi, Yong Zhang, Xi Zhou, Li Ran, Jining Yang, Jun-dong Zhu, Qian-yong Zhang, Man-tian Mi. Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota. mBio, April 2016 DOI: 10.1128/mBio.02210-15

 

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Man-tian Mi (2016). Resveratrol Attenuates Atherosclerosis Through Actions on Gut Microbiome MedicalResearch.com

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