Zheng Wang1, Brandilyn A Peters1, Mykhaylo Usyk2, Jiaqian Xing1, David B Hanna1, Tao Wang1, Wendy S Post3, Alan L Landay4, Howard N Hodis5, Kathleen Weber6, Audrey French7, Elizabeth T Golub8, Jason Lazar9, Deborah Gustafson10, Seble Kassaye11, Bradley Aouizerat12, Sabina Haberlen8, Carlos Malvestutto13, Matthew Budoff14, Steven M Wolinsky15, Anjali Sharma16, Kathryn Anastos1,16, Clary B Clish17, Robert C Kaplan1,18, Robert D Burk1,2,19, Qibin Qi1,20. 1. Department of Epidemiology and Population Health (Z.W., B.A.P., J.X., D.B.H., T.W., K.A., R.C.K., R.D.B., Q.Q.), Albert Einstein College of Medicine, Bronx, New York. 2. Department of Pediatrics (M.U., R.D.B.), Albert Einstein College of Medicine, Bronx, New York. 3. Department of Medicine, Johns Hopkins University, Baltimore, MD (W.S.P.). 4. Department of Internal Medicine, Rush University Medical Center, Chicago, IL (A.L.L). 5. Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles (H.N.H.). 6. Hektoen Institute of Medicine, Chicago, IL (K.W.). 7. Department of Internal Medicine, John H. Stroger Jr Hospital of Cook County, Chicago, IL (A.F.). 8. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (E.T.G., S.H.). 9. Department of Medicine (J.L.), State University of New York Downstate Medical Center, Brooklyn. 10. Department of Neurology (D.G.), State University of New York Downstate Medical Center, Brooklyn. 11. Department of Medicine, Georgetown University, Washington DC (S.K.). 12. College of Dentistry, New York University (B.A.). 13. Wexner Medical Center, Ohio State University, Columbus (C.M.). 14. David Geffen School of Medicine, University of California, Los Angeles (M.B.). 15. Department of Medicine, Feinberg School of Medicine, Northwestern University Chicago, IL (S.M.W.). 16. Department of Medicine (A.S., K.A.), Albert Einstein College of Medicine, Bronx, New York. 17. Broad Institute of MIT and Harvard, Cambridge, MA (C.B.C.). 18. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (R.C.K.). 19. Department of Microbiology & Immunology (R.D.B.), Albert Einstein College of Medicine, Bronx, New York. 20. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (Q.Q.).
Abstract
BACKGROUND: Alterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection. METHODS: We analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up. RESULTS: We found 2 potentially pathogenic bacteria, Fusobacterium and Proteus, were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09-1.64] and 1.24 [1.02-1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines. CONCLUSIONS: Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.
BACKGROUND: Alterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection. METHODS: We analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up. RESULTS: We found 2 potentially pathogenic bacteria, Fusobacterium and Proteus, were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09-1.64] and 1.24 [1.02-1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines. CONCLUSIONS: Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.
Authors: Omry Koren; Aymé Spor; Jenny Felin; Frida Fåk; Jesse Stombaugh; Valentina Tremaroli; Carl Johan Behre; Rob Knight; Björn Fagerberg; Ruth E Ley; Fredrik Bäckhed Journal: Proc Natl Acad Sci U S A Date: 2010-10-11 Impact factor: 11.205
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Authors: Amnon Amir; Daniel McDonald; Jose A Navas-Molina; Evguenia Kopylova; James T Morton; Zhenjiang Zech Xu; Eric P Kightley; Luke R Thompson; Embriette R Hyde; Antonio Gonzalez; Rob Knight Journal: mSystems Date: 2017-03-07 Impact factor: 6.496