Gut microbiota, circulating inflammatory markers and metabolites, and carotid artery atherosclerosis in HIV infection

Microbiome

Research

Howard N. Hodis¹  Clary B. Clish²  Brandilyn A. Peters³  David B. Hanna³  Tao Wang³  Zheng Wang³  Kathryn Anastos⁴  Qibin Qi⁵  Robert D. Burk⁶  Robert C. Kaplan⁷  Elizabeth T. Golub⁸  Alan L. Landay⁹  Audrey French^1,10  Anjali Sharma^1,11  Wendy S. Post^1,12  Jason Lazar^1,13  Deborah Gustafson^1,14  Christopher C. Sollecito^1,15  Evan Grassi^1,15  Mykhaylo Usyk^1,15  Fanua Wiek^1,15  Lauren St. Peter^1,15  MacKenzie Bryant^1,16  Tara Schwartz^1,16  Rob Knight^1,17  Kathleen M. Weber^1,18 

[1] Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;Broad Institute of MIT and Harvard, Cambridge, MA, USA;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Obstetrics & Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Obstetrics & Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA;Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA;Department of Internal Medicine, Stroger Hospital of Cook County, Chicago, IL, USA;Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Medicine, Johns Hopkins University, Baltimore, MD, USA;Department of Medicine, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA;Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA;Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Pediatrics, University of California, La Jolla, San Diego, CA, USA;Department of Pediatrics, University of California, La Jolla, San Diego, CA, USA;Department of Bioengineering, University of California, La Jolla, San Diego, CA, USA;Department of Computer Science and Engineering, University of California, La Jolla, San Diego, CA, USA;Center for Microbiome Innovation, University of California, La Jolla, San Diego, CA, USA;Hektoen Institute of Medicine, Chicago, IL, USA;

关键词: Gut microbiota;    Inflammatory markers;    Metabolomics;    Atherosclerosis;    HIV infection;   

DOI  :  10.1186/s40168-023-01566-2

 received in 2022-11-02, accepted in 2023-05-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAlterations in gut microbiota have been implicated in HIV infection and cardiovascular disease. However, how gut microbial alterations relate to host inflammation and metabolite profiles, and their relationships with atherosclerosis, have not been well-studied, especially in the context of HIV infection. Here, we examined associations of gut microbial species and functional components measured by shotgun metagenomics with carotid artery plaque assessed by B-mode carotid artery ultrasound in 320 women with or at high risk of HIV (65% HIV +) from the Women’s Interagency HIV Study. We further integrated plaque-associated microbial features with serum proteomics (74 inflammatory markers measured by the proximity extension assay) and plasma metabolomics (378 metabolites measured by liquid chromatography tandem mass spectrometry) in relation to carotid artery plaque in up to 433 women.ResultsFusobacterium nucleatum, a potentially pathogenic bacteria, was positively associated with carotid artery plaque, while five microbial species (Roseburia hominis, Roseburia inulinivorans, Johnsonella ignava, Odoribacter splanchnicus, Clostridium saccharolyticum) were inversely associated with plaque. Results were consistent between women with and without HIV. Fusobacterium nucleatum was positively associated with several serum proteomic inflammatory markers (e.g., CXCL9), and the other plaque-related species were inversely associated with proteomic inflammatory markers (e.g., CX3CL1). These microbial-associated proteomic inflammatory markers were also positively associated with plaque. Associations between bacterial species (especially Fusobacterium nucleatum) and plaque were attenuated after further adjustment for proteomic inflammatory markers. Plaque-associated species were correlated with several plasma metabolites, including the microbial metabolite imidazole-propionate (ImP), which was positively associated with plaque and several pro-inflammatory markers. Further analysis identified additional bacterial species and bacterial hutH gene (encoding enzyme histidine ammonia-lyase in ImP production) associated with plasma ImP levels. A gut microbiota score based on these ImP-associated species was positively associated with plaque and several pro-inflammatory markers.ConclusionAmong women living with or at risk of HIV, we identified several gut bacterial species and a microbial metabolite ImP associated with carotid artery atherosclerosis, which might be related to host immune activation and inflammation.C3iH5Kb-7Cp2aWsNqgxHA4Video Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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