Zheng Wang1, Mykhaylo Usyk2, Christopher C Sollecito2, Yunping Qiu3, Jessica Williams-Nguyen4, Simin Hua1, Ana Gradissimo2, Tao Wang1, Xiaonan Xue1, Irwin J Kurland3, Klaus Ley5,6, Alan L Landay7, Kathryn Anastos1,3,8, Rob Knight6,9,10,11, Robert C Kaplan1,4, Robert D Burk1,2,8,12, Qibin Qi1. 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
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.
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.
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