Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection
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Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PWH (SNF-1–3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower α-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-associated metabolites in PWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging.
Originalsprog | Engelsk |
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Artikelnummer | e82785 |
Tidsskrift | eLife |
Vol/bind | 12 |
Antal sider | 25 |
ISSN | 2050-084X |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The study is funded by the Swedish Research Council grants 2017-01330, 2018-06156, and 2021-01756 to U.N. Novo Nordic Foundation, Lundbeck Foundation, Augustinus Foundation, Region
Funding Information:
Hovedstaden, and Rigshospitalet Research Council to SDN. DDM acknowledges the support received from Danish National Research Foundation Grant 126 (DNRF126).
Publisher Copyright:
© 2023, eLife Sciences Publications Ltd. All rights reserved.
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