Altered Gut Microbiota and Host Metabolite Profiles in Women With Human Immunodeficiency Virus

Author:

Wang Zheng1ORCID,Usyk Mykhaylo2,Sollecito Christopher C2,Qiu Yunping3,Williams-Nguyen Jessica4,Hua Simin1,Gradissimo Ana2,Wang Tao1,Xue Xiaonan1,Kurland Irwin J3,Ley Klaus56,Landay Alan L7,Anastos Kathryn138,Knight Rob691011,Kaplan Robert C14,Burk Robert D12812,Qi Qibin1

Affiliation:

1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA

2. Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA

3. Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA

4. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

5. Division of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, California, USA

6. Department of Bioengineering, University of California, San Diego, La Jolla, California, USA

7. Department of Internal Medicine, Rush Medical College, Chicago, Illinois, USA

8. Department of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, New York, USA

9. Department of Pediatrics, University of California, San Diego, La Jolla, California, USA

10. Center for Microbiome Innovation, University of California, San Diego, La Jolla, California, USA

11. Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California, USA

12. Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA

Abstract

Abstract Background Alterations in gut microbiota (GMB) and host metabolites have been noted in individuals with HIV. However, it remains unclear whether alterations in GMB and related functional groups contribute to disrupted host metabolite profiles in these individuals. Methods This study included 185 women (128 with longstanding HIV infection, 88% under antiretroviral therapy; and 57 women without HIV from the same geographic location with comparable characteristics). Stool samples were analyzed by 16S rRNA V4 region sequencing, and GMB function was inferred by PICRUSt. Plasma metabolomic profiling was performed using liquid chromatography–tandem mass spectrometry, and 133 metabolites (amino acids, biogenic amines, acylcarnitines, and lipids) were analyzed. Results Four predominant bacterial genera were identified as associated with HIV infection, with higher abundances of Ruminococcus and Oscillospira and lower abundances of Bifidobacterium and Collinsella in women with HIV than in those without. Women with HIV showed a distinct plasma metabolite profile, which featured elevated glycerophospholipid levels compared with those without HIV. Functional analyses also indicated that GMB lipid metabolism was enriched in women with HIV. Ruminococcus and Oscillospira were among the top bacterial genera contributing to the GMB glycerophospholipid metabolism pathway and showed positive correlations with host plasma glycerophospholipid levels. One bacterial functional capacity in the acetate and propionate biosynthesis pathway was identified to be mainly contributed by Bifidobacterium; this functional capacity was lower in women with HIV than in women without HIV. Conclusions Our integrative analyses identified altered GMB with related functional capacities that might be associated with disrupted plasma metabolite profiles in women with HIV.

Funder

National Heart, Lung, and Blood Institute

Feldstein Medical Foundation Research

National Institute of Mental Health

Metabolomics Core Facility of the Einstein-Mount Sinai Diabetes Research and Training Center of the Albert Einstein College of Medicine

National Institute of Allergy and Infectious Diseases

Einstein Cancer Research Center

Einstein Liver Research Center

National Cancer Institute

University of Alabama at Birmingham

Atlanta WIHS

University of North Carolina

Connie Wofsy Women’s HIV Study

WIHS Data Management and Analysis Center

Southern California WIHS

WIHS

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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