Gut Microbial-Related Choline Metabolite Trimethylamine-N-Oxide Is Associated With Progression of Carotid Artery Atherosclerosis in HIV Infection

We examined associations of 5 plasma choline metabolites with carotid plaque among 520 HIV-infected and 217 HIV-uninfected participants (112 incident plaque cases) over 7 years. After multivariable adjustment, higher gut microbiota-related metabolite trimethylamine-N-oxide (TMAO) was associated with an increased risk of carotid plaque in HIV-infected participants (risk ratio = 1.25 per standard deviation increment; 95% confidence interval, 1.05-1.50; P = .01). TMAO was positively correlated with biomarkers of monocyte activation and inflammation (sCD14, sCD163). Further adjustment for these biomarkers attenuated the association between TMAO and carotid plaque (P = .08). Among HIV-infected individuals, plasma TMAO was associated with carotid atherosclerosis progression, partially through immune activation and inflammation.

[1]  Sanjiv J. Shah,et al.  Plasma Tryptophan-Kynurenine Metabolites Are Altered in Human Immunodeficiency Virus Infection and Associated With Progression of Carotid Artery Atherosclerosis , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  Mardge H. Cohen,et al.  Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men , 2017, The Journal of infectious diseases.

[3]  I. Rosenberg,et al.  Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults. , 2017, The American journal of clinical nutrition.

[4]  J. Margolick,et al.  Brief Report: Intestinal Microbiota-Produced Trimethylamine-N-Oxide and Its Association With Coronary Stenosis and HIV Serostatus , 2016, Journal of acquired immune deficiency syndromes.

[5]  A. Kjær,et al.  Microbiota-Dependent Marker TMAO Is Elevated in Silent Ischemia but Is Not Associated With First-Time Myocardial Infarction in HIV Infection , 2016, Journal of acquired immune deficiency syndromes.

[6]  K. Anastos,et al.  HIV Infection Is Associated With Progression of Subclinical Carotid Atherosclerosis. , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  D. Gauguier,et al.  Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine , 2015, AIDS.

[8]  B. Palmer,et al.  HIV-induced alteration in gut microbiota , 2014, Gut microbes.

[9]  S. Hazen,et al.  Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. , 2013, The New England journal of medicine.

[10]  K. Kraemer,et al.  HIV status, burden of comorbid disease, and biomarkers of inflammation, altered coagulation, and monocyte activation. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  E. Rosenberg,et al.  Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. , 2011, The Journal of infectious diseases.

[12]  Brian J. Bennett,et al.  Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease , 2011, Nature.

[13]  S. Zeisel,et al.  Choline: an essential nutrient for public health. , 2009, Nutrition reviews.

[14]  M. Lederman,et al.  Microbial translocation is a cause of systemic immune activation in chronic HIV infection , 2006, Nature Medicine.

[15]  R H Selzer,et al.  The Role of Carotid Arterial Intima-Media Thickness in Predicting Clinical Coronary Events , 1998, Annals of Internal Medicine.