HomeCirculationVol. 143, No. 20From the Literature Free AccessNewsPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessNewsPDF/EPUBFrom the Literature Tracy HamptonPhD Tracy HamptonTracy Hampton Search for more papers by this author Originally published17 May 2021https://doi.org/10.1161/CIRCULATIONAHA.121.055221Circulation. 2021;143:2023–2024The Gut Microbiome, Diet, and Cardiometabolic RiskNew research published in Nature Medicine indicates that the impact of the Mediterranean diet (MedDiet) on cardiometabolic disease risk may be affected by an individual’s gut microbes.In analyses of 307 male participants in the Health Professionals Follow-Up Study, investigators assessed cardiometabolic disease risk through blood biomarkers of glucose homeostasis, lipid metabolism, and inflammation, and they quantified each participant’s adherence to the MedDiet on the basis of dietary information collected every 4 years across nearly 3 decades. They also profiled participants’ gut microbiomes from stool analyses from up to 4 time points per individual and identified the microbial enzymes and pathways that were activated to varying degrees on the basis of adherence to the MedDiet.The protective link between the MedDiet and participants’ cardiometabolic disease risk was strongest in those with gut microbiomes depleted of Prevotella copri, a common gut bacterium that has been both positively and negatively associated with health in different populations.“Because of the observational nature of our study, we cannot distinguish between two alternate hypotheses: (1) in individuals who do not carry Pcopri, the gut microbiome may metabolize components of the MedDiet more efficiently and effectively, leading to higher yields of cardioprotective chemical products, or (2) individuals who adhere to the MedDiet are less likely to acquire or retain Pcopri, which is then itself independently cardioprotective,” the authors wrote.The team also found that the gut microbiomes of individuals with greater adherence to the MedDiet tended to be enriched with several major dietary fiber metabolizers, including Faecalibacterium prausnitzii and Bacteroides cellulosilyticus, as well as their functions that break down specific dietary fibers, such as pectin. Such individuals also exhibited depletions of Clostridium leptum, Collinsella aerofaciens, and related functions, including secondary bile acid production.The findings suggest that dietary interventions or recommendations aimed at preventing cardiometabolic disease could be tailored to individuals’ gut microbial profiles.Wang DD et al. The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk. Nat Med. 2021;27:333–343. doi: 10.1038/s41591-020-01223-3Download figureDownload PowerPointNew research indicates that differences in individuals’ gut microbes might modify the interaction between diet and cardiometabolic health.Network-Correcting Therapeutic Candidate for Heart Valve DiseaseClinical researchers have been working to gain a better understanding of the gene regulatory networks—sets of genes that interact with each other to control specific cell functions—that drive disease. Doing so could point to new treatment strategies that target core disease mechanisms.Now, in a study published in Science, investigators have used a branch of artificial intelligence called machine learning to identify small molecules that broadly correct gene networks that are dysregulated in a human-induced pluripotent stem cell model of a common form of heart disease involving the aortic valve.“Our study harnessed machine learning and stem cell technology to learn how the gene network in heart valves is disrupted in calcific aortic valve disease—a leading cause of heart disease where the valves harden over time, preventing appropriate blood flow from the heart—and to identify therapeutics that could restore the gene network back to a healthy state,” said senior author Dr Deepak Srivastava, of the Gladstone Institute of Cardiovascular Disease and University of California San Francisco.Dr Srivastava noted that drugs are usually tested for their effects on only one or a few genes or characteristics in a disease, but his team took an approach that tested drugs for their effects on the gene network as a whole—a strategy that may point to drugs that are more likely to treat core disease mechanisms rather than symptoms.The most promising candidate that surfaced after screening nearly 1600 small molecules against disease-relevant stem cells was effective in correcting the gene network in cells from a broad panel of patients with sporadic aortic valve disease. This top drug candidate, called XCT790, also effectively prevented and treated heart valve disease in mice. “We next plan to pursue further preclinical safety and dosage studies on a path toward a clinical trial in humans,” said Dr Srivastava. “Preventing the progressive hardening of heart valves that occurs in calcific aortic valve disease could avoid the need for tens of thousands of valve transplants annually in the United States alone.”The work also provides a promising network-based drug testing framework that can be applied to other human diseases.Theodoris CV et al. Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease. Science. 2021;371:eabd0724. doi: 10.1126/science.abd0724A Newly Discovered Genetic Arrhythmia SyndromeInvestigators have identified a previously unrecognized and potentially life-threatening genetic arrhythmia syndrome that develops secondary to rare genetic variations in the gene coding for the cardiac ryanodine receptor. This receptor, which is located on the sarcoplasmic reticulum within cardiomyocytes, controls intracellular calcium release and muscle contraction in the heart.In a study published in Science Translational Medicine involving clinical, genetic, and functional analyses, researchers identified the condition as cardiac ryanodine receptor calcium release deficiency syndrome (CRDS). The team found that loss-of-function mutations in the cardiac ryanodine receptor in families of individuals who experienced sudden cardiac death were linked to cardiac arrhythmias. The group also developed a CRDS diagnostic test involving a programmed electric stimulation protocol, and they found that treatment with the currently available antiarrhythmic drugs quinidine and flecainide could suppress ventricular arrhythmias in a CRDS mouse model.“Previously, when CRDS patients suffered cardiac arrests, no cause for their near fatal—or potentially fatal—events could be identified, and they were often given a cryptic label of idiopathic ventricular fibrillation. Recognition of the existence of CRDS will enable physicians to correctly identify the cause of cardiac arrest in these patients,” said senior author Dr S.R. Wayne Chen, of the University of Calgary, in Canada. “Although more work is still required to clarify optimal approaches to diagnosis and treatment, we are hopeful that proper diagnosis will enable doctors to intervene and protect patients before they have life threatening events. Because it is a genetic disorder, proper diagnosis can also enable identification of potentially vulnerable family members so that they can also be protected from dangerous arrhythmias.”Sun B et al. Cardiac ryanodine receptor calcium release deficiency syndrome. Sci Transl Med. 2021;13:eaba7287. doi: 10.1126/scitranslmed.aba7287 nFootnoteshttps://www.ahajournals.org/journal/circ Previous Back to top Next FiguresReferencesRelatedDetails May 18, 2021Vol 143, Issue 20Article InformationMetrics Download: 449 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.121.055221 Originally publishedMay 17, 2021 PDF download